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Sample records for deoxyglucose

  1. Dephosphorylation of 2-deoxyglucose 6-phosphate and 2-deoxyglucose export from cultured astrocytes.

    Science.gov (United States)

    Forsyth, R J; Bartlett, K; Eyre, J

    1996-03-01

    Neurotransmitter-stimulated mobilization of astrocyte glycogen has been proposed as a basis for local energy homeostasis in brain. However, uncertainty remains over the fate of astrocyte glycogen. Upon transfer of cultured astrocytes pre-loaded with [2-3H]2-deoxyglucose 6-phosphate at non-tracer concentrations to a glucose-free, 2-deoxyglucose-free medium, rapid dephosphorylation of a proportion of the intracellular 2-deoxyglucose 6-phosphate pool and export of 2-deoxyglucose to the extracellular fluid occurs. Astrocytes show very low, basal rates of gluconeogenesis from pyruvate (approx. 1 nmol mg protein-1 h-1). Astrocytes in vivo may be capable of physiologically significant glucose export from glucose-6-phosphate. The low gluconeogenic activity in astrocytes suggests that the most likely source of glucose-6-phosphate may be glycogen. These findings support the hypothesis that export, as glucose, to adjacent neurons may be one of the possible fate(s) of astrocytic glycogen. Such export of glycogen as glucose occurring in response to increases in neuronal activity could contribute to energy homeostasis on a paracrine scale within brain.

  2. [3H]-2-Deoxyglucose autoradiography in a molluscan nervous system

    International Nuclear Information System (INIS)

    Reingold, S.C.; Sejnowski, T.J.; Gelperin, A.

    1981-01-01

    The authors have used [ 3 H]2-deoxyglucose autoradiography to correlate the labeling of individual neurons with electrical activity within the central nervous system of a terrestrial mollusc, Limax maximus. In an electrically quiescent control preparation where a single neuron is impaled with a glass microelectrode but not stimulated, several somata are uniformly labeled at 3-5 times background. In preparations where a single cell is impaled and stimulated, one or more somata are heavily labeled with [ 3 H]2-deoxyglucose at 10-50 times tissue background. This technique may be useful for surveying metabolically active neurons during spontaneous and driven electrical activity. (Auth.)

  3. Differential labelling of retinal neurones by 3H-2-deoxyglucose

    International Nuclear Information System (INIS)

    Basinger, S.F.; Gordon, W.C.; Lam, D.M.K.

    1979-01-01

    The use of tritium-labelled 2-deoxyglucose in combination with plastic embedding is reported to produce stimulus dependent labelling at cellular level in the isolated goldfish retina. The results suggest that the use of tritium in place of the more usual 14 C labelled tracer is advantageous in studying the physiology and functional connections of retinal neurones. (U.K.)

  4. A critical appraisal of semi-quantitative analysis of 2-deoxyglucose autoradiograms

    International Nuclear Information System (INIS)

    Kelly, P.T.; McCulloch, J.

    1983-01-01

    Semi-quantitative analysis (e.g. optical density ratios) of [ 14 C]2-deoxyglucose autoradiograms is widely used in neuroscience research. The authors demonstrate that a fixed ratio of 14 C-concentrations in the CNS does not yield a constant optical density ratio but is dependent upon the exposure time in the preparation of the autoradiograms and the absolute amounts of 14 C from which the concentration ratio is derived. The failure of a fixed glucose utilization ratio to result in a constant optical density ratio represents a major interpretative difficulty in investigations where only semi-quantitative analysis of [ 14 C]2-deoxyglucose autoradiograms is undertaken. (Auth.)

  5. Critical appraisal of semi-quantitative analysis of 2-deoxyglucose autoradiograms

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, P T; McCulloch, J [Glasgow Univ. (UK)

    1983-06-13

    Semi-quantitative analysis (e.g. optical density ratios) of (/sup 14/C)2-deoxyglucose autoradiograms is widely used in neuroscience research. The authors demonstrate that a fixed ratio of /sup 14/C-concentrations in the CNS does not yield a constant optical density ratio but is dependent upon the exposure time in the preparation of the autoradiograms and the absolute amounts of /sup 14/C from which the concentration ratio is derived. The failure of a fixed glucose utilization ratio to result in a constant optical density ratio represents a major interpretative difficulty in investigations where only semi-quantitative analysis of (/sup 14/C)2-deoxyglucose autoradiograms is undertaken.

  6. A functional study of the rat olfactory bulb through autoradiography with 14C-2-deoxyglucose

    International Nuclear Information System (INIS)

    Verrier, Marie; Leveteau, Jean; Giachetti, Ismene; MacLeod, Patrick

    1978-01-01

    The autoradiographic methods has been used in the rat to map active regions in the olfactory bulb after a pulse of 14 C-2-deoxyglucose with electrical stimulation of the lateral olfactory tract. The highest optical densities were found at the external plexiform, mural, internal plexiform and granular layers: the lowest was found in the glomerular layer [fr

  7. 2-deoxyglucose as a selective agent for derepressed mutants of Pichia stipitis

    Science.gov (United States)

    Hassan K. Sreenath; Thomas W. Jeffries

    1998-01-01

    The glucose analog 2-deoxyglucose (2-DOG) has been used to obtain mutants derepressed for pentose metabolism. Some researchers have used 2-DOG alone whereas others have used it in the presence of a glucoserepressible carbon source. We examined both methods and screened mutant strains for improved use of xylose in the presence of glucose. Pichia stipitis mutants...

  8. Ethanol fermentation of beet molasses by a yeast resistant to distillery waste water and 2-deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Tadenuma, Makoto; Shimoi, Hitoshi; Sato, Shun' ichi; Moriya, Kazuhito; Saito, Kazuo [National Research Inst. of Brewing, Tokyo, Japan Hokkaido Sugar Co., Ltd., Tokyo (Japan) Sendai Regional Taxation Bureau, Sendai (Japan)

    1989-05-25

    A flocculent killer yeast, strain H-1 selected for ethanol fermentation of beet molasses, has a tendency to lose its viability in distillery waste water (DWW) of beet molasses mash after ethanol fermentation. Through acclimations of strain H-1 in DWW, strain W-9, resistant to DWW, was isolated. Strain M-9, resistant to 2-deoxyglucose was further isolated through acclimations of strain W-9 in medium containing 150 ppm 2-deoxyglucose. A fermentaion test of beet molasses indicated that the ethanol productivity and suger consumption were improved by strain M-9 compared with the parental strain H-1 and strain W-9. The concentration of ethanol produced by strain M-9 was 107.2 g/1, and concentration of residual sugars, which were mainly composed of sucrose and fructose, were lower than those produced by the parental strain H-9 and strain W-9 at the end of fermentation of beet molasses. 6 refs., 2 figs., 2 tabs.

  9. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Dyve, S [Department of General Physiology and Biophysics, Panum Institute, Copenhagen (Denmark); Gjedde, A [Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal, Quebec (Canada)

    1991-01-01

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +- 2 {mu}mol hg{sup -1} min{sup -1}. (author).

  10. Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity.

    Science.gov (United States)

    Taylor, M D; Roberts, A D; Nickles, R J

    1996-07-01

    We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[18F]fluoro-2-deoxyglucose (2-[18F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[18F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[18F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 +/- 4% (72 +/- 5%, decay corrected, synthesis time = 31 min).

  11. Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity

    International Nuclear Information System (INIS)

    Taylor, M.D.; Roberts, A.D.; Nickles, R.J.

    1996-01-01

    We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[ 18 F]fluoro-2-deoxyglucose (2-[ 18 F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[ 18 F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[ 18 F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 ± 4% (72 ± 5%, decay corrected, synthesis time = 31 min)

  12. Double-label autoradiographic deoxyglucose method for sequential measurement of regional cerebral glucose utilization

    Energy Technology Data Exchange (ETDEWEB)

    Redies, C; Diksic, M; Evans, A C; Gjedde, A; Yamamoto, Y L

    1987-08-01

    A new double-label autoradiographic glucose analog method for the sequential measurement of altered regional cerebral metabolic rates for glucose in the same animal is presented. This method is based on the sequential injection of two boluses of glucose tracer labeled with two different isotopes (short-lived /sup 18/F and long-lived /sup 3/H, respectively). An operational equation is derived which allows the determination of glucose utilization for the time period before the injection of the second tracer; this equation corrects for accumulation and loss of the first tracer from the metabolic pool occurring after the injection of the second tracer. An error analysis of this operational equation is performed. The double-label deoxyglucose method is validated in the primary somatosensory (''barrel'') cortex of the anesthetized rat. Two different rows of whiskers were stimulated sequentially in each rat; the two periods of stimulation were each preceded by an injection of glucose tracer. After decapitation, dried brain slices were first exposed, in direct contact, to standard X-ray film and then to uncoated, ''tritium-sensitive'' film. Results show that the double-label deoxyglucose method proposed in this paper allows the quantification and complete separation of glucose utilization patterns elicited by two different stimulations sequentially applied in the same animal.

  13. [14C]2-deoxyglucose uptake in ground squirrel brain during hibernation

    International Nuclear Information System (INIS)

    Kilduff, T.S.; Sharp, F.R.; Heller, H.C.

    1982-01-01

    Autoradiographic patterns of [14C]2-deoxyglucose uptake are described throughout the brains of hibernating and euthermic ground squirrels. Autoradiographs of the brains of hibernating animals are generally homogeneous in comparison to euthermic animals; hence, the relative 2-deoxyglucose uptake (R2DGU) of gray to white matter for the majority of the 85 neural structures examined decreases during hibernation. Two categories of structures are identified as potentially important in hibernation: (1) structures that have the highest R2DGU during hibernation (cochlear nucleus, paratrigeminal nucleus, and superior colliculus) and (2) structures that undergo the least reduction in R2DGU in the transition from euthermia to hibernation (suprachiasmatic nucleus and lateral septal nucleus). The percentage of reduction in R2DGU that a structure undergoes in the transition from euthermia to hibernation is proportional to the R2DGU of that structure during euthermia. The suprachiasmatic, paratrigeminal, and cochlear nuclei undergo less of a reduction than would be predicted from this relationship and may be particularly important during hibernation. Sensory nuclei that receive primary afferent projections are among the structures with the highest R2DGU during hibernation. These metabolically active structures may be responsible for the sensitivity of the hibernator to environmental stimuli

  14. Symmetric increased skeletal muscular uptake of 18F fluoro-deoxyglucose: a clue for the diagnosis of Graves' disease

    International Nuclear Information System (INIS)

    Santhosh, Sampath; Mittal, Bhagwant Rai; Kashyap, Raghava; Bhattacharya, Anish; Singh, Baljinder

    2011-01-01

    18 F fluoro-deoxyglucose (FDG) uptake in the thyroid and thymus is well reported in patients with Grave's disease. Incidental skeletal muscle uptake has also been reported in other non-musculoskeletal (benign and malignant) pathologies. We report a patient of Grave's disease showing symmetrical skeletal muscle uptake but no thyroidal or thymus uptake of FDG. (author)

  15. Mapping of odor-related neuronal activity in the olfactory bulb by high-resolution 2-deoxyglucose autoradiography

    International Nuclear Information System (INIS)

    Lancet, D.; Greer, C.A.; Kauer, J.S.; Shepherd, G.M.

    1982-01-01

    The spatial distribution of odor-induced neuronal activity in the olfactory bulb, the first relay station of the olfactory pathway, is believed to reflect important aspects of chemosensory coding. We report here the application of high-resolution 2-deoxyglucose autoradiography to the mapping of spatial patterns of metabolic activity at the level of single neurons in the olfactory bulb. It was found that glomeruli, which are synaptic complexes containing the first synaptic relay, tend to be uniformly active or inactive during odor exposure. Differential 2-deoxyglucose uptake was also observed in the somata of projection neurons (mitral cells) and interneurons (periglomerular and granule cells). This confirms and extends our previous studies in which odor-specific laminar and focal uptake patterns were revealed by the conventional x-ray film 2-deoxyglucose method due to Sokoloff and colleagues [Sokoloff, L., Reivich, M., Kennedy, C., DesRosiers, M. H., Patlak, C. S., Pettigrew, K. D., Sakurada, O. and Shinohara, M. (1977) J. Neurochem. 28, 897-916]. Based on results obtained by the two methods, it is suggested that the glomerulus as a whole serves as a functional unit of activity. The high-resolution results are interpreted in terms of the well-characterized synaptic organization of the olfactory bulb and also serve to illustrate the capability of the 2-deoxyglucose autoradiographic technique to map metabolic activity in single neurons of the vertebrate central nervous system

  16. 18F-deoxyglucose-PET in the detection of recurrence in head and neck cancer

    International Nuclear Information System (INIS)

    Chen Yingrui; Li Weixiong; Gu Meixin; Xie Songxi

    2002-01-01

    Objective: To evaluate 18 F-deoxyglucose-positron emission tomography (FDG-PET) in the detection of suspicious recurrence in head and neck cancers, as compared with CT/MRI imaging. Methods: Thirty-seven patients with clinically suspicious recurrences in head and neck cancers underwent FDG-PET, with 34 checked with CT/MRI imaging. The final diagnosis of recurrence were proved by pathology or clinical following-up. Results: FDG-PET detected recurrence successfully in 32 of 37 (86.5%) patients with 3 false positives and 2 false negatives. The FDG-PET sensitivity, specificity and accuracy in defining local recurrence were 91.7%, 76.9%, 86.5%, respectively; and those of CT/MRI were 68.2%, 75.0%, 61.8%, respectively. Conclusion: In comparison with CT/MRI, FDG-PET possesses a high accuracy in detecting recurrence in head and neck cancers

  17. [High gene conversion frequency between genes encoding 2-deoxyglucose-6-phosphate phosphatase in 3 Saccharomyces species].

    Science.gov (United States)

    Piscopo, Sara-Pier; Drouin, Guy

    2014-05-01

    Gene conversions are nonreciprocal sequence exchanges between genes. They are relatively common in Saccharomyces cerevisiae, but few studies have investigated the evolutionary fate of gene conversions or their functional impacts. Here, we analyze the evolution and impact of gene conversions between the two genes encoding 2-deoxyglucose-6-phosphate phosphatase in S. cerevisiae, Saccharomyces paradoxus and Saccharomyces mikatae. Our results demonstrate that the last half of these genes are subject to gene conversions among these three species. The greater similarity and the greater percentage of GC nucleotides in the converted regions, as well as the absence of long regions of adjacent common converted sites, suggest that these gene conversions are frequent and occur independently in all three species. The high frequency of these conversions probably result from the fact that they have little impact on the protein sequences encoded by these genes.

  18. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    International Nuclear Information System (INIS)

    Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

    1981-01-01

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc

  19. Positron imaging feasibility studies: characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms

    International Nuclear Information System (INIS)

    Larson, S.M.; Weiden, P.L.; Grunbaum, J.

    1981-01-01

    Uptake of [ 3 H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studies. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both between individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic processes of tumors, including glycolysis

  20. Hemiballismus: Study of a case using positron emission tomography with 18fluoro-2-deoxyglucose

    International Nuclear Information System (INIS)

    Dubinsky, R.M.; Greenberg, M.; Di Chiro, G.; Baker, M.; Hallett, M.

    1989-01-01

    A 64-year-old man had right-sided persistent hemiballismus. Cerebral computed tomography (CT) and 0.5-T magnetic resonance imaging (MRI) showed no abnormalities, but 1.5-T MRI showed decreased signal intensity of the putamina, greater on the left than on the right. The subthalamic area was normal on CT and MRI. Positron emission tomography with 18fluoro2-deoxyglucose showed marked hypometabolism of the left putamen (60% of the right) and hypermetabolism of the left parietal lobe (138% of the right). The decreased metabolism of the left putamen may indicate a reduction in neuronal firing. The pathophysiology of the hemiballismus in this case may be loss of tonic inhibition of the lateral globus pallidus from the putamen, leading in turn to greater inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, and less inhibition of the thalamus and motor cortex, and thus allowing expression of the ballistic movements

  1. Mapping of functional activity in brain with 18F-fluoro-deoxyglucose

    International Nuclear Information System (INIS)

    Alavi, A.; Reivich, M.; Greenberg, J.

    1981-01-01

    The efficacy of using the 18 F-fluoro-deoxyglucose ( 18 F-DG) for measuring regional cerebral glucose utilization in man during functional activation is demonstrated. Normal male volunteers subjected to sensory stimuli (visual, auditory, tactile) exhibited focal increases in glucose metabolism in response to the stimulus. Unilateral visual hemifield stimulation caused the contralateral striate cortex to become more active metabolically than the striate cortex ipsilateral to the stimulated hemifield. Similarly, stroking of the fingers and hand of one arm with a brush produced an increase in metabolism in the contralateral postcentral gyrus compared to the homologous ipsilateral region. The auditory stimulus, which consisted of monaural listening to either a meaningful or nonmeaningful story, caused an increase in glucose metabolism in the right temporal cortex independent of which ear was stimulated. These results demonstrate that the 18 F-DG technique is capable of providing functional maps in vivo in the human brain

  2. Uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus

    International Nuclear Information System (INIS)

    Richards, H.K.; Bucknall, R.M.; Jones, H.C.; Pickard, J.D.

    1989-01-01

    The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days

  3. Adaptation of the deoxyglucose method for use at cellular level: histological processing of the central nervous system for high resolution radio-autography

    International Nuclear Information System (INIS)

    Des Rosiers, M.H.; Descarries, Laurent

    1978-01-01

    Vascular perfusion of all products required for primary fixation, postfixation, dehydration and embedding of nervous tissue in Epon permits radio-autographic detection of radioactivity accumulated in the central nervous system after intravenous injection of [ 3 H]deoxyglucose. This histological technique should allow application of the deoxyglucose method at cellular if not subcellular level, since a high proportion of the tracer appears to be retained in situ in specimens adequately preserved for light and electron microscope radio-autography [fr

  4. Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

    Science.gov (United States)

    Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

    2013-02-01

    In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.

  5. Suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14C-labeled deoxyglucose

    International Nuclear Information System (INIS)

    Reppert, S.M.; Schwartz, W.J.

    1984-01-01

    The circadian clock located in the suprachiasmatic nuclei (SCN) was characterized in the fetal rat by using 14 C-labeled deoxyglucose to monitor glucose utilization (metabolic activity) of the nuclei. A clear day-night oscillation of metabolic activity was detectable in the fetal SCN from the 19th through the 21st days of gestation; the nuclei were metabolically active during the subjective day and metabolically inactive during the subjective night. During the subjective day on gestational day 21, the fetal SCN were found to manifest high metabolic activity for most of the subjective day. The authors were able to acutely dissociate SCN metabolic activity in the mother rat from that in the fetus by exposing the pregnant animals to light during the normal dark period of diurnal lighting on gestational day 20. The results show the utility of the deoxyglucose method for directly investigating prenatally the function of the biological clock located in the SCN

  6. Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors

    OpenAIRE

    Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

    2012-01-01

    Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sa...

  7. The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in resectable pancreatic cancer.

    Science.gov (United States)

    Crippa, Stefano; Salgarello, Matteo; Laiti, Silvia; Partelli, Stefano; Castelli, Paola; Spinelli, Antonello E; Tamburrino, Domenico; Zamboni, Giuseppe; Falconi, Massimo

    2014-08-01

    The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in pancreatic ductal adenocarcinoma is debated. We retrospectively assessed the value of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in addition to conventional imaging as a staging modality in pancreatic cancer. (18)Fluoro-deoxyglucose positron emission tomography/computed tomography was performed in 72 patients with resectable pancreatic carcinoma after multi-detector computed tomography positron emission tomography was considered positive for a maximum standardized uptake value >3. Overall, 21% of patients had a maximum standardized uptake value ≤ 3, and 60% of those had undergone neoadjuvant treatment (P=0.0001). Furthermore, 11% of patients were spared unwarranted surgery since positron emission tomography/computed tomography detected metastatic disease. All liver metastases were subsequently identified with contrast-enhanced ultrasound. Sensitivity and specificity of positron emission tomography/computed tomography for distant metastases were 78% and 100%. The median CA19.9 concentration was 48.8 U/mL for the entire cohort and 292 U/mL for metastatic patients (P=0.112). The widespread application of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in patients with resectable pancreatic carcinoma seems not justified. It should be considered in selected patients at higher risk of metastatic disease (i.e. CA19.9>200 U/mL) after undergoing other imaging tests. Neoadjuvant treatment is significantly associated with low metabolic activity, limiting the value of positron emission tomography in this setting. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Caloric restriction mimetic 2-deoxyglucose maintains cytoarchitecture and reduces tau phosphorylation in primary culture of mouse hippocampal pyramidal neurons.

    Science.gov (United States)

    Bele, M S; Gajare, K A; Deshmukh, A A

    2015-06-01

    Typical form of neurons is crucially important for their functions. This is maintained by microtubules and associated proteins like tau. Hyperphosphorylation of tau is a major concern in neurodegenerative diseases. Glycogen synthase kinase3β (GSK3β) and cyclin-dependent protein kinase 5 (Cdk5) are the enzymes that govern tau phosphorylation. Currently, efforts are being made to target GSK3β and Cdk5 as possible therapeutic avenues to control tau phosphorylation and treat neurodegenerative diseases related to taupathies. In a number of studies, caloric restriction mimetic 2-deoxyglucose (C6H12O5) was found to be beneficial in improving the brain functions. However, no reports are available on the effect of 2-deoxyglucose 2-DG on tau phosphorylation. In the present study, hippocampal pyramidal neurons from E17 mouse embryos were isolated and cultured on poly-L-lysine-coated coverslips. Neurons from the experimental group were treated with 10 mM 2-deoxyglucose. The treatment of 2-DG resulted in healthier neuronal morphology in terms of significantly lower number of cytoplasmic vacuoles, little or no membrane blebbings, maintained axon hillock and intact neurites. There were decreased immunofluorescence signals for GSK3β, pTau at Ser262, Cdk5 and pTau at Ser235 suggesting decreased tau phosphorylation, which was further confirmed by Western blotting. The results indicate the beneficial effects of 2-DG in controlling the tau phosphorylation and maintaining the healthy neuronal cytoarchitecture.

  9. Relationship between CNS metabolism and cytoarchitecture: a review of 14C-deoxyglucose studies with correlation to cytochrome oxidase histochemistry

    International Nuclear Information System (INIS)

    Di Rocco, R.J.; Kageyama, G.H.; Wong-Riley, M.T.

    1989-01-01

    Since the inception of the 14 C-deoxyglucose method and its extension to in vivo imaging of regional cerebral glucose metabolism in humans by positron emission tomography, uncertainty has persisted concerning the type of work to which regional metabolism is coupled, as well as the distribution of this work within the neuron. 14 C-deoxyglucose studies indicate that functionally-coupled neural metabolism is more apparent in axon terminals and perhaps dendrites than neuronal perikarya. Moreover, it appears that most of the metabolism in axon terminals is accounted for by Na+-K+-ATPase activity. Nevertheless, cytochrome oxidase histochemistry reveals the presence of intensely reactive mitochondria in soma-dendrite regions opposite presynaptic axon terminals, thereby indicating that continuous temporal and spatial summation of postsynaptic graded potentials is associated with increased metabolism. While the situation concerning the relative postsynaptic metabolic prices of EPSP's and IPSP's remains uncertain, the presence of elevated levels of cytochrome oxidase activity within certain classes of presynaptic terminals indicates that active excitation and inhibition is associated with increases in presynaptic metabolism. This observation has been confirmed in 14 C-deoxyglucose studies. Nevertheless, studies of neonatal hippocampus indicate that, before metabolic activity shifts to dendritic and telodendritic regions of electrophysiological activity, metabolism is high in somal foci of biosynthesis. 51 references

  10. Glycolytic inhibitors 2-deoxyglucose and 3-bromopyruvate synergize with photodynamic therapy respectively to inhibit cell migration.

    Science.gov (United States)

    Feng, Xiaolan; Wang, Pan; Liu, Quanhong; Zhang, Ting; Mai, Bingjie; Wang, Xiaobing

    2015-06-01

    Most cancer cells have the specially increased glycolytic phenotype, which makes this pathway become an attractive therapeutic target. Although glycolytic inhibitor 2-deoxyglucose (2-DG) has been demonstrated to potentiate the cytotoxicity of photodynamic therapy (PDT), the impacts on cell migration after the combined treatment has never been reported yet. The present study aimed to analyze the influence of glycolytic inhibitors 2-DG and 3-bromopyruvate (3-BP) combined with Ce6-PDT on cell motility of Triple Negative Breast Cancer MDA-MB-231 cells. As determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium-bromide-Tetraz-olium (MTT) assay, more decreased cell viability was observed in 2-DG + PDT and 3-BP + PDT groups when compared with either monotherapy. Under optimal conditions, synergistic potentiation on cell membrane destruction and the decline of cell adhesion and cells migratory ability were observed in both 2-DG + PDT and 3-BP + PDT by electron microscope observation (SEM), wound healing and trans-well assays. Besides, serious microfilament network collapses as well as impairment of matrix metalloproteinases-9 (MMP-9) were notably improved after the combined treatments by immunofluorescent staining. These results suggest that 2-DG and 3-BP can both significantly potentiated Ce6-PDT efficacy of cell migration inhibition.

  11. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  12. [Chilean experience with the use of 18F-deoxyglucose positron emission tomography].

    Science.gov (United States)

    Massardo, Teresa; Jofré, M Josefina; Sierralta, Paulina; Canessa, José; González, Patricio; Humeres, Pamela; Valdebenito, Robert

    2007-03-01

    Clinical oncology is the main application of 18F-deoxyglucose (FDG) positron emission tomography (PET). To evaluate the first 1,000 patients studied with FDG PET in Chile. Retrospective analysis of 1,000 patients (aged between 1 and 94 years, 550 females) studied with FDG PET, since 2003. All studies were performed in a high resolution Siemens Ecat-Exact HR (+). All reports were based on the visual analysis of three plane and three-dimensional images. Ninety seven percent of exams were done for oncological indications, mainly lung lesions, lymphoma, colorectal and gastroesophageal, cancer and breast tumors. Only 1% of patients had brain tumors. Non tumor neurological indications corresponded to 1.7%. Cardiac studies were only 0.3% and inflammatory process corresponded to 1%. The 5.6% corresponded to pediatric population. Six percent of patients were aged less than 18 years and in 50% of them, the indication was oncological, mainly lymphomas, brain tumors, endocrine cancers and sarcomas. The remaining 50% had a neurological indications, mainly for refractory epilepsy. PET FDG imaging was effective in the management of diverse diseases of children and adults.

  13. Correlation of PET and AMS analyses for early kinetics of 2-fluoro-2-deoxyglucose (FDG)

    International Nuclear Information System (INIS)

    Minamimoto, Ryogo; Hamabe, Yoshimi; Miyaoka, Teiji; Theeraladanon, Chumpol; Oka, Takashi; Matsui, Takao; Inoue, Tomio

    2010-01-01

    The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground 14 C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient (r) of the measurements using PET ( 18 F-FDG) and AMS ( 14 C-FDG) were quite high at 0.97 (Y = 7.54E - 05X + 0.02, p 18 F-FDG was nearly identical with that of 14 C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method.

  14. A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2-deoxyglucose in human plasma.

    Science.gov (United States)

    Gounder, Murugesan K; Lin, Hongxia; Stein, Mark; Goodin, Susan; Bertino, Joseph R; Kong, Ah-Ng Tony; DiPaola, Robert S

    2012-05-01

    2-Deoxyglucose (2-DG), an analog of glucose, is widely used to interfere with glycolysis in tumor cells and studied as a therapeutic approach in clinical trials. To evaluate the pharmacokinetics of 2-DG, we describe the development and validation of a sensitive HPLC fluorescent method for the quantitation of 2-DG in plasma. Plasma samples were deproteinized with methanol and the supernatant was dried at 45°C. The residues were dissolved in methanolic sodium acetate-boric acid solution. 2-DG and other monosaccharides were derivatized to 2-aminobenzoic acid derivatives in a single step in the presence of sodium cyanoborohydride at 80°C for 45 min. The analytes were separated on a YMC ODS C₁₈ reversed-phase column using gradient elution. The excitation and emission wavelengths were set at 360 and 425 nm. The 2-DG calibration curves were linear over the range of 0.63-300 µg/mL with a limit of detection of 0.5 µg/mL. The assay provided satisfactory intra-day and inter-day precision with RSD less than 9.8%, and the accuracy ranged from 86.8 to 110.0%. The HPLC method is reproducible and suitable for the quantitation of 2-DG in plasma. The method was successfully applied to characterize the pharmacokinetics profile of 2-DG in patients with advanced solid tumors. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Correlation of PET and AMS analyses for early kinetics of 2-fluoro-2-deoxyglucose (FDG)

    Science.gov (United States)

    Minamimoto, Ryogo; Hamabe, Yoshimi; Miyaoka, Teiji; Theeraladanon, Chumpol; Oka, Takashi; Matsui, Takao; Inoue, Tomio

    2010-04-01

    The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground 14C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient ( r) of the measurements using PET ( 18F-FDG) and AMS ( 14C-FDG) were quite high at 0.97 ( Y = 7.54 E - 05 X + 0.02, p blood clearance profile of 18F-FDG was nearly identical with that of 14C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method.

  16. Correlation of PET and AMS analyses for early kinetics of 2-fluoro-2-deoxyglucose (FDG)

    Energy Technology Data Exchange (ETDEWEB)

    Minamimoto, Ryogo, E-mail: ryogom@yokohama-cu.ac.j [Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama (Japan); Hamabe, Yoshimi; Miyaoka, Teiji [Institute of Accelerator Analysis (IAA) Ltd., Kawasaki (Japan); Theeraladanon, Chumpol; Oka, Takashi [Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama (Japan); Matsui, Takao [Institute of Accelerator Analysis (IAA) Ltd., Kawasaki (Japan); Inoue, Tomio [Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama (Japan)

    2010-04-15

    The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground {sup 14}C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient (r) of the measurements using PET ({sup 18}F-FDG) and AMS ({sup 14}C-FDG) were quite high at 0.97 (Y = 7.54E - 05X + 0.02, p < 0.001). The blood clearance profile of {sup 18}F-FDG was nearly identical with that of {sup 14}C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method.

  17. 2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium.

    Science.gov (United States)

    Haggstrom, Lucy R; Nelson, Julia A; Wegner, Eva A; Caplan, Gideon A

    2017-11-01

    Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolism is fundamentally disturbed; however, it has not been investigated using 2- 18 F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucose metabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a key region for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned during delirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participants during delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p delirium duration. This research found widespread, reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium.

  18. Test-retest studies of cerebral glucose metabolism using fluorine-18 deoxyglucose: validation of method

    International Nuclear Information System (INIS)

    Brooks, R.A.; Di Chiro, G.; Zukerberg, B.W.; Bairamian, D.; Larson, S.M.

    1987-01-01

    In studies using [ 18 F]deoxyglucose (FDG), one often wants to compare metabolic rates following stimulation (drug or motor-sensory) with the baseline values. However, because of reproducibility problems with baseline variations of 25% in the same individual not uncommon, the global effect of the stimulation may be difficult to see. One approach to this problem is to perform the two studies sequentially. This means that, with the 110-min half-life of 18 F, one must take into account the residual activity from the first study when calculating metabolic rates for the second. We performed TEST-RETEST baseline studies on four subjects, with a 1-hr interval between injections. These studies were done without stimulation, in order to validate the repeatability of the method. To reduce the amount of residual activity from the first study, the first injection was only 2 mCi in three cases, and only 1 mCi in one case, out of a total injected dose of 5 mCi. A correction for residual activity was included in the RETEST calculation of metabolic rate. The results showed a global metabolic shift between the two studies of 2% to 9%. An error analysis shows that the shift could be further reduced if anatomically comparable scans are done at comparable postinjection times

  19. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man.

  20. Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin.

    Science.gov (United States)

    Kim, Eui Hyun; Lee, Ji-Hyun; Oh, Yoonjee; Koh, Ilkyoo; Shim, Jin-Kyoung; Park, Junseong; Choi, Junjeong; Yun, Mijin; Jeon, Jeong Yong; Huh, Yong Min; Chang, Jong Hee; Kim, Sun Ho; Kim, Kyung-Sup; Cheong, Jae-Ho; Kim, Pilnam; Kang, Seok-Gu

    2017-02-01

    Deprivation of tumor bioenergetics by inhibition of multiple energy pathways has been suggested as an effective therapeutic approach for various human tumors. However, this idea has not been evaluated in glioblastoma (GBM). We hypothesized that dual inhibition of glycolysis and oxidative phosphorylation could effectively suppress GBM tumorspheres (TS). Effects of 2-deoxyglucose (2DG) and metformin, alone and in combination, on GBM-TS were evaluated. Viability, cellular energy metabolism status, stemness, invasive properties, and GBM-TS transcriptomes were examined. In vivo efficacy was tested in a mouse orthotopic xenograft model. GBM-TS viability was decreased by the combination of 2DG and metformin. ATP assay and PET showed that cellular energy metabolism was also decreased by this combination. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TS were also significantly suppressed by combined treatment with 2DG and metformin. A transcriptome analysis showed that the expression levels of stemness- and epithelial mesenchymal transition-related genes were also significantly downregulated by combination of 2DG and metformin. Combination treatment also prolonged survival of tumor-bearing mice and decreased invasiveness of GBM-TS. The combination of 2DG and metformin effectively decreased the stemness and invasive properties of GBM-TS and showed a potential survival benefit in a mouse orthotopic xenograft model. Our findings suggest that targeting TS-forming cells by this dual inhibition of cellular bioenergetics warrants expedited clinical evaluation for the treatment of GBM. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. Rolipram depresses [{sup 3}H]2-deoxyglucose uptake in mouse brain and heart in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Megumi; Hosoi, Rie; Kobayashi, Kaoru; Inoue, Osamu [Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita-shi, Osaka (Japan); Nishimura, Tsunehiko [Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2002-09-01

    The effects of systemic administration of rolipram, a selective phosphodiesterase type 4 inhibitor, on [{sup 3}H]2-deoxyglucose (DG) uptake in brain and peripheral tissues were examined. Rolipram significantly and dose-dependently decreased [{sup 3}H]DG uptake in brain, heart and skeletal muscle. In contrast, the radioactivity concentrations in the plasma of rolipram-treated mice were significantly higher than those of control mice at all times after injection of the tracer. In the kinetic study, the initial uptake of [{sup 3}H]DG in brain was decreased by rolipram, whereas no significant differences were observed in the uptake in heart and skeletal muscle. However, radioactivity concentrations in the brain, heart and skeletal muscle 30 min after the injection of [{sup 3}H]DG were significantly lowered by rolipram to about 60%, 10% and 10% of control values, respectively. The uptake of [{sup 13}N]ammonia in brain and heart of rolipram-treated mice was slightly decreased, which indicated that rolipram diminished both cerebral and cardiac blood flow. These results indicate that the phosphorylation process via hexokinase rather than the transport of [{sup 3}H]DG might be depressed by rolipram. Together with the previous observations that inhibition of protein kinase A (PKA) markedly enhanced [{sup 14}C]DG uptake in rat brain, these results indicate an important role of the cAMP/PKA systems in the regulation of glucose metabolism in the living brain as well as in peripheral tissues such as the heart and skeletal muscle. (orig.)

  2. Resolution-limiting factors in 2-deoxyglucose autoradiography. I. Factors other than diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Gallistel, C.R.; Nichols, S. (Pennsylvania Univ., Philadelphia, PA (USA). Dept. of Psychology)

    1983-05-16

    The authors measured the extent to which factors other than the diffusion of the radioactive label during tissue preparation limits the spatial resolving power of 2-deoxyglucose (2-DG) autoradiography. Radioactive swept frequency gratings were created using microcircuit lithography. The gratings consisted of alternating equal width radioactive and non-radioactive bars in groups of narrowing bar width (effective range 500-20 ..mu..m). The vertical thickness of the gratings ranged from 2.25 to 20 ..mu..m. The isotope in the radioactive bars was either /sup 14/C or /sup 3/H. A variety of X-ray films were exposed to these gratings and the resulting images scanned with microdensitometers or video digitizers to determine the fall off in image contrast (dark-bar values minus light-bar values) as a function of the number of dark bars (lines) per millimeter. The power of the isotope was the resolution limiting factor. Grating thickness and type of film made little difference. The limit of resolution with /sup 14/C was 10 lines/mm: with /sup 3/H it was 25 lines/mm. The microdensitometer itself is apt to be a resolution limiting factor; the resolving power of those commonly used in autoradiography is unlikely to exceed 10 lines/mm. From measurements of the steepness of gray-matter to white-matter transitions in the image from a tissue section, they conclude that the resolution in the image was no worse than 1.6-3.2 lines/mm. Either the isotope or diffusion of the 2-DG during tissue preparation must be the factor that limits resolution.

  3. Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Tada, Masao; Yamada, Susumu; Hori, Katsuyoshi; Saito, Sachiko; Sato, Kazunori; Fukuda, Hiroshi; Iwata, Ren; Ido, Tatsuo

    1999-01-01

    To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14 C-2-deoxyglucose (2DG) and 14 C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy. (orig.)

  4. Additive Effects of Millimeter Waves and 2-Deoxyglucose Co-Exposure on the Human Keratinocyte Transcriptome.

    Science.gov (United States)

    Soubere Mahamoud, Yonis; Aite, Meziane; Martin, Catherine; Zhadobov, Maxim; Sauleau, Ronan; Le Dréan, Yves; Habauzit, Denis

    2016-01-01

    Millimeter Waves (MMW) will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD) of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed. We tested the effects of MMWs on cell metabolism by co-treating MMW-exposed cells with a glycolysis inhibitor, 2-deoxyglucose (2dG, 20 mM for 3 hours), and whole genome expression was evaluated along with the ATP content. We found that the 2dG treatment decreased the cellular ATP content and induced a high modification in the transcriptome (632 coding genes). The affected genes were associated with transcriptional repression, cellular communication and endoplasmic reticulum homeostasis. The MMW/2dG co-treatment did not alter the keratinocyte ATP content, but it did slightly alter the transcriptome, which reflected the capacity of MMW to interfere with the bioenergetic stress response. The RT-PCR-based validation confirmed 6 MMW-sensitive genes (SOCS3, SPRY2, TRIB1, FAM46A, CSRNP1 and PPP1R15A) during the 2dG treatment. These 6 genes encoded transcription factors or inhibitors of cytokine pathways, which raised questions regarding the potential impact of long-term or chronic MMW exposure on metabolically stressed cells.

  5. Additive Effects of Millimeter Waves and 2-Deoxyglucose Co-Exposure on the Human Keratinocyte Transcriptome.

    Directory of Open Access Journals (Sweden)

    Yonis Soubere Mahamoud

    Full Text Available Millimeter Waves (MMW will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed. We tested the effects of MMWs on cell metabolism by co-treating MMW-exposed cells with a glycolysis inhibitor, 2-deoxyglucose (2dG, 20 mM for 3 hours, and whole genome expression was evaluated along with the ATP content. We found that the 2dG treatment decreased the cellular ATP content and induced a high modification in the transcriptome (632 coding genes. The affected genes were associated with transcriptional repression, cellular communication and endoplasmic reticulum homeostasis. The MMW/2dG co-treatment did not alter the keratinocyte ATP content, but it did slightly alter the transcriptome, which reflected the capacity of MMW to interfere with the bioenergetic stress response. The RT-PCR-based validation confirmed 6 MMW-sensitive genes (SOCS3, SPRY2, TRIB1, FAM46A, CSRNP1 and PPP1R15A during the 2dG treatment. These 6 genes encoded transcription factors or inhibitors of cytokine pathways, which raised questions regarding the potential impact of long-term or chronic MMW exposure on metabolically stressed cells.

  6. Investigation of 18F-2-deoxyglucose for the measure of myocardial glucose metabolism

    International Nuclear Information System (INIS)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.R.; Kuhl, D.E.

    1977-01-01

    18 F labeled 2-deoxyglucose ( 18 FDG) was studied as a glucose analog. Myocardial uptake and retention, blood clearance, species (dog, monkey, man) dependence and effect of diet on uptake were investigated. Normal myocardial uptake of 18 FDG was 3 to 4% in dog and monkey and 1 to 4% of injected dose in man compared to brain uptake of 2% in dog, 5 to 6% in monkey and 4 to 8% in man. The metabolic rate (MR) for glucose in non-fasting (glycolytic state) was 2.8 times greater than in fasting (ketogenic state). Human subjects showed higher myocardial uptake after a normal meal than after meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t 1 / 2 of 0.2 to 0.3 min followed by a t 1 / 2 of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had a t 1 / 2 of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. High image contrast ratios between heart and blood (dog 3.5/1; man 14/1), heart and lung (dog 9/1; man 20/1), heart and liver (dog 15/1; man 10/1) were found with the ECAT positron tomograph. 18 FDG was found to be rapidly taken up by the myocardium without any significant tissue clearance over a 4 hour period. 18 FDG is transported, phosphorylated to 18 FDG-6-PO 4 and trapped in myocardial cells in the same manner as has been found for brain and exhibits excellent imaging properties. Determination of glucose and FFA MR in vivo with ECT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

  7. Investigation of [18F]2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    International Nuclear Information System (INIS)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-01-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

  8. Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Cristiane de Oliveira

    Full Text Available Studying the uptake of 2-deoxy glucose (2-DG analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor during mild and severe biliary AP.Wistar rats (300 g; 8-12/group were administered NIR 2-DG (10 nM; I.V.. Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g within 10 minutes of giving NIR 2-DG. Controls (CON only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP.NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality

  9. The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells

    International Nuclear Information System (INIS)

    Jeon, Jeong Yong; Kim, Seung Won; Park, Ki Cheong; Yun, Mijin

    2015-01-01

    Recent reports using metabolism regulating drugs showed that nutrient deprivation was an efficient tool to suppress cancer progression. In addition, autophagy control is emerging to prevent cancer cell survival. Autophagy breaks down the unnecessary cytoplasmic components into anabolic units and energy sources, which are the most important sources for making the ATP that maintains homeostasis in cancer cell growth and survival. Therefore, the glucose analog 2-deoxyglucose (2DG) has been used as an anticancer reagent due to its inhibition of glycolysis. Prostate cancer cells (PC3) were treated with 2DG for 6 h or 48 h to analyze the changing of cell cycle and autophagic flux. Rapamycin and LC3B overexpressing vectors were administered to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells to analyze PC3 cells growth and survival. The samples for western blotting were prepared in each culture condition to confirm the expression level of autophagy related and regulating proteins. We demonstrated that 2DG inhibits PC3 cells growth and had discriminating effects on autophagy regulation based on the different time period of 2DG treatment to control cell survival. Short-term treatment of 2DG induced autophagic flux, which increased microtubule associated protein 1 light chain 3B (LC3B) conversion rates and reduced p62 levels. However, 2DG induced autophagic flux is remarkably reduced over an extended time period of 2DG treatment for 48 h despite autophagy inducing internal signaling being maintained. The relationship between cell growth and autophagy was proved. Increased autophagic flux by rapamycin or LC3B overexpression powerfully reduced cell growth, while autophagy inhibition with shBeclin1 plasmid or chloroquine had no significant effect on regulating cell growth. Given these results, maintaining increased autophagic flux was more effective at inhibiting cancer cell progression than inhibition of

  10. [Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors].

    Science.gov (United States)

    Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

    2012-09-01

    The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

  11. Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors

    International Nuclear Information System (INIS)

    Massardo, Teresa; Jofre, Maria Josefina; Sierralta, Maria Paulina; Canessa, Jose; Castro, Gabriel; Berrocal, Isabel; Gallegos, Ivan

    2012-01-01

    Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. Results: FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. Conclusions: PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control

  12. [Usefulness of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography in evaluation of gastric cancer stage].

    Science.gov (United States)

    Yoon, Na Ri; Park, Jae Myung; Jung, Hee Sun; Cho, Yu Kyung; Lee, In Seok; Choi, Myung Gyu; Chung, In Sik; Song, Kyo Young; Park, Cho Hyun

    2012-05-01

    The usefulness of ¹⁸F-fluoro-2-deoxyglucose (FDG)-PET in detecting primary cancer, lymph node metastasis, and distant metastasis were studied in the gastric cancer patients. The subjects were 392 gastric cancer patients who received FDG-PET and an abdominal CT test prior to surgery. The results of FDG-PET and CT were compared with the surgical and pathologic results. The primary site detection rate of FDG-PET was 74.4%, 50.3% in early gastric cancer and 92.0% in advanced gastric cancer. Detection rate was higher when tumors were larger than 3.5 cm, had deeper depth of invasion, and at a later stage (pusefullness of FDG-PET is limited to the advanced stage. Diagnostic value of this test was not superior to CT. However, FDG-PET may be useful in detecting synchronous double primary cancers.

  13. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

    International Nuclear Information System (INIS)

    Gonzales-Lima, F.

    1986-01-01

    The autoradiographic ( 14 C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. (author)

  14. Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro-Deoxyglucose-Positron Emission Tomography/Computed Tomography

    International Nuclear Information System (INIS)

    Aparici, Carina Mari; Win, Aung Zaw

    2015-01-01

    The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated colon adenocarcinoma in the right ascending colon. A presurgical staging 18-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) found increased metabolic activity in the cervical, axillary, mediastinal, supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of metastasis was very unusual for lynch syndrome associated colon adenocarcinoma and the involvement of those lymph nodes resembles the pattern of spread of lymphoma. He underwent right hemicolectomy and he was subsequently treated with 12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful imaging modality in following-up the treatment response in colon adenocarcinoma

  15. A difference in [14C]deoxyglucose autoradiographic patterns in striate cortex between Macaca and Saimiri monkeys following monocular stimulation

    International Nuclear Information System (INIS)

    Hendrickson, A.E.; Wilson, J.R.

    1979-01-01

    Since the apparent absence of ocular dominance columns (ODC) in some New World primates could be caused by deficiencies of the transsynaptic autoradiographic technique, such as spillage of label in the poorly laminated dorsal lateral geniculate nucleus, the authors have examined this question using a functional autoradiographic tracing technique based on the uptake of [ 14 C]2-deoxyglucose ([ 14 C]dG) by active neurons. When only one eye is stimulated, this innovative method graphically demonstrates a repetitive pattern in Macaca monkey striate cortex which has been interpreted to be the ODC driven by the open eye. They now report on the results of a comparative study of Old World Macaca and New World Saimiri monkeys using [ 14 C]dG autoradiography in which evidence is found for repetitive patterns of [ 14 C]dG in Saimiri for layers above, but not in, layer IV. (Auth.)

  16. Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    International Nuclear Information System (INIS)

    Sharp, F.R.; Gonzalez, M.F.

    1984-01-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

  17. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales-Lima, F

    1986-04-24

    The autoradiographic (/sup 14/C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. 12 refs.

  18. Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Marwick, T.H.; MacIntyre, W.J.; Salcedo, E.E.; Go, R.T.; Saha, G.; Beachler, A.

    1991-01-01

    The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. Increased post-exercise FDG uptake, appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization

  19. 14C-2-deoxyglucose uptake in the ground squirrel brain during entrance to and arousal from hibernation

    International Nuclear Information System (INIS)

    Kilduff, T.S.; Miller, J.D.; Radeke, C.M.; Sharp, F.R.; Heller, H.C.

    1990-01-01

    Neuronal activity underlying various phases of the mammalian hibernation cycle was investigated using the 14 C-2-deoxyglucose (2DG) method. Relative 2DG uptake (R2DGU) values were computed for 96 brain regions across 7 phases of the hibernation cycle: euthermia, 3 body temperature (Tb) intervals during entrance into hibernation, stable deep hibernation, and 2 Tb intervals during arousal from hibernation. Multivariate statistical techniques were employed to identify objectively groups of brain regions whose R2DGU values showed a similar pattern across all phases of hibernation. Factor analysis revealed that most of the variability in R2DGU values for the 96 brain regions across the entire cycle could be accounted for by 3 principal factors. These factors could accurately discriminate the various phases of hibernation on the basis of the R2DGU values alone. Three hypothalamic and 3 cortical regions were identified as possibly mediating the entrance into hibernation because they underwent a change in R2DGU early in entrance into hibernation and loaded strongly on one of the principal factors. Another 4 hypothalamic regions were similarly identified as possibly causally involved in the arousal from hibernation. These results, coupled with characteristic changes in ordinal rank of the 96 brain regions in each phase of hibernation, support the concept that mammalian hibernation is an active, integrated orchestration of neurophysiological events rather than a state entered through a passive process

  20. Plastic reorganization in the inferior colliculus of the immature mouse studied by 14C$deoxyglucose method

    International Nuclear Information System (INIS)

    Taniguchi, Ikuo; Saito, Nozomu

    1978-01-01

    Plastic reinnervation was observed in the mouse by means of autoradiography with [ 14 C]deoxyglucose (DG). It is possible that the ipsilateral inhibitory pathway for input from the cochlea to the inferior colliculus (IC) switches to excitation or disinhibition following unilateral cochlear destruction. Autoradiographs of the brains of mice exposed to sound stimuli exhibited high optical densities in activated regions due to the increased uptake of DG. IC revealed essentially the same optical density on both sides. No bilateral asymmetry appeared in autoradiographs of IC in 46-day-old normal animals with binaural hearing, indicating glucose consumption at the same rate bilaterally at the level of IC in normal animals. On the 1st and 4th days after destruction of the left cochles, the contralateral IC exhibited less labeling than the ipsilateral IC. However, optical density in the contralateral IC increase. On the 11th day, it was apparently reduced in bilateral asymmetry. Autoradiographs on the 18th day demonstrated essentially an equal uptake of DG on both sides and almost the same pattern as in normal animals. These changes suggested postoperative reorganization possible occurred as a result of reinnervation of the input fibers to IC via the commissure of inferior colliculi (COM) or the lateral lemniscus ipsilaterally. COM was transectioned 31 days after destruction of the left cochlea. IC demonstrated symmetrical uptake of DG on both sides. (J.P.N.)

  1. Relation between thallium-201/iodine 123-BMIPP subtraction and fluorine 18 deoxyglucose polar maps in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ito, Y; Hasegawa, S; Yamaguchi, H; Yoshioka, J; Uehara, T; Nishimura, T

    2000-01-01

    Clinical studies have shown discrepancies in the distribution of thallium-201 and iodine 123-beta-methyl-iodophenylpentadecanoic acid (BMIPP) in patients with hypertrophic cardiomyopathy (HCM). Myocardial uptake of fluorine 18 deoxyglucose (FDG) is increased in the hypertrophic area in HCM. We examined whether the distribution of a Tl-201/BMIPP subtraction polar map correlates with that of an FDG polar map. We normalized to maximum count each Tl-201 and BMIPP bull's-eye polar map of 6 volunteers and obtained a standard Tl-201/BMIPP subtraction polar map by subtracting a normalized BMIPP bull's-eye polar map from a normalized Tl-201 bull's-eye polar map. The Tl-201/BMIPP subtraction polar map was then applied to 8 patients with HCM (mean age 65+/-12 years) to evaluate the discrepancy between Tl-201 and BMIPP distribution. We compared the Tl-201/BMIPP subtraction polar map with an FDG polar map. In patients with HCM, the Tl-201/BMIPP subtraction polar map showed a focal uptake pattern in the hypertrophic area similar to that of the FDG polar map. By quantitative analysis, the severity score of the Tl-201/BMIPP subtraction polar map was significantly correlated with the percent dose uptake of the FDG polar map. These results suggest that this new quantitative method may be an alternative to FDG positron emission tomography for the routine evaluation of HCM.

  2. The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

    Science.gov (United States)

    Deonarine, P; Han, S; Poon, F W; de Wet, C

    2013-08-01

    Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

  3. Significance of local cerebral glucose utilization determined by the autoradiographic (/sup 14/C)deoxyglucose method in experimentally induced coma

    Energy Technology Data Exchange (ETDEWEB)

    Sakurada, O.; Kobayashi, M.; Ueno, H.; Ishii, S. (Juntendo Univ., Tokyo (Japan). School of Medicine)

    1982-01-01

    Bilateral lesions made in the midbrain reticular formation of the rat produced behavioral akinesia. These animals neither ate nor drank. EEGs of these animals usually showed high voltage slow waves at rest. Slight EEG arousal response was demonstrated by clapping, touching and pinching only in rats with moderate impairment. Concerning the rates of local cerebral glucose utilization (LCGU) measured by means of the autoradiographic (/sup 14/C) deoxyglucose method, 13 structures exhibited significant reductions in 28 gray structures examined when compared with sham operated rats. Lesions in the midbrain reticular formation resulted in reduction of LCGU in the neocortex, ventral nucleus of the thalamus, subthalamic nucleus, and medial and lateral geniculated bodies, mamillary body, septal nucleus and caudateputamen. Structures which did not show any significant change in LCGU were those related to the paleo and archi-cortices. These findings suggest the existence of two types of ascending activating systems. Administration of 30 mg/kg of pentobarbital reduced LCGU diffusely throughout the brain. When thyrotropin releasing hormone (TRH) was administered to rats with lesions in the midbrain reticular formation, reversal of the reduction of LCGU was observed in the dorsomedial nucleus of the thalamus and the mamillary body. Reversal of LCGU in the dorsomedial nucleus of thalamus was especially significant and its level exceeded the level of the sham control value. This suggests TRH might exert its function through the dorsomedial nucleus of the thalamus and mamillary body. When TRH was administered to rats treated with pentobarbital, significant reversal was observed in the following structures: the lateral and ventral nucleus of the thalamus, dentate gyrus, caudate-putamen, nucleus accumbens, pontine gray matter, and raphe nucleus.

  4. Chronic effects of dietary carbohydrate variation on [18F]-2-fluoro-2-deoxyglucose uptake in rodent heart.

    Science.gov (United States)

    Fine, Eugene J; Miao, Weibing; Koba, Wade; Volek, Jeff S; Blaufox, M Donald

    2009-09-01

    Measured cardiac [F]-2-fluoro-2-deoxyglucose (FDG) activity in human PET scans is variable despite efforts to standardize patient preparation. Heart uptake can obscure chest disease, and is of physiologic interest. Short-term carbohydrate (CHO) restriction can reduce FDG uptake, although unreliably, whereas long-term restriction of CHO has not been systematically studied. It would be valuable to understand FDG hearts' chronic dietary dependence. Fifteen Wistar rats (age 4 weeks) were randomized to three diet groups (n = 5) of low (0.1% of total energy), intermediate (52%), and high (78%) CHO content (LC, IC, and HC, respectively). After 4 weeks, blood for ketone bodies (KB), glucose, insulin, and glucagon was obtained, followed in 2 days by whole-body PET with 37 MBq FDG. Diet groups were switched every 4 weeks to control for the effects of dietary order. Heart maximal standardized uptake value was compared among animals. Heart mean maximal standardized uptake value was dramatically reduced for LC (3.4+/-0.4; P<0.001) compared with either IC (10.9+/-0.7) or HC (11.0+/-0.7) (P=NS, IC vs. HC). KB (mumol/l) differed widely (P<0.001) in LC (718.6+/-40.0) versus IC (120.3+/-34.0) and HC (99.2+/-32.1) (P=NS, IC vs. HC), whereas glucose, insulin, and glucagon did not differ among the groups. Sustained CHO-restriction results in marked, reproducibly reduced cardiac FDG uptake. Six-fold to seven-fold increased KB concentrations provide alternative substrate to glucose.

  5. Common fur and mystacial vibrissae parallel sensory pathways: 14C 2-deoxyglucose and WGA-HRP studies in the rat

    International Nuclear Information System (INIS)

    Sharp, F.R.; Gonzalez, M.F.; Morgan, C.W.; Morton, M.T.; Sharp, J.W.

    1988-01-01

    Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex

  6. Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

    2011-01-01

    This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

  7. 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

    2017-05-01

    Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

  8. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose

    International Nuclear Information System (INIS)

    Cooney, G.J.; Astbury, L.D.; Williams, P.F.; Caterson, I.D.

    1987-01-01

    The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of [1- 14 C]2-deoxyglucose 6-phosphate and blood disappearance rate of [1- 14 C]2-deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was the most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice

  9. Simultaneous estimates of regional myocardial blood flow and metabolism by the developing chick heart using [201]thallium and [14C] 2-deoxyglucose autoradiography

    International Nuclear Information System (INIS)

    Kostreva, D.R.; Wood, J.D.

    1990-01-01

    Little is known about regional myocardial blood flow and metabolism in the developing heart. Simultaneous estimates of regional myocardial blood flow and glucose metabolism have been made in the adult rat by Yonekura et al using [ 201 ] Thallium (THAL) and [ 14 C]2-deoxyglucose (DG) autoradiography. Since glucose is the primary cardiac metabolic substrate during development, glucose utilization is also an estimate of myocardial metabolism. Examination and comparison of the THAL and DG autoradiographs revealed that there is an uncoupling of blood flow and metabolism in the developing chick heart. Areas of the heart which had marked glucose utilization did not always have marked blood flow. Regions of the heart which had marked blood flow but very little glucose utilization were the interventricular septum and the apex. One explanation for this disparity is that although blood flow may be established in these regions, normal cardiac function requiring significant substrate utilization may not be fully developed

  10. Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Song, Yoo Sung; Lee, Won Woo; Lee, Jong Seok; Kim, Sang Eun

    2015-11-01

    Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan-Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients.

  11. Evaluation on the effectiveness of 2-deoxyglucose-6-phosphate phosphatase (DOGR1) gene as a selectable marker for oil palm (Elaeis guineensis Jacq.) embryogenic calli transformation mediated by Agrobacterium tumefaciens

    Science.gov (United States)

    Izawati, Abang Masli Dayang; Masani, Mat Yunus Abdul; Ismanizan, Ismail; Parveez, Ghulam Kadir Ahmad

    2015-01-01

    DOGR1, which encodes 2-deoxyglucose-6-phosphate phosphatase, has been used as a selectable marker gene to produce transgenic plants. In this study, a transformation vector, pBIDOG, which contains the DOGR1 gene, was transformed into oil palm embryogenic calli (EC) mediated by Agrobacterium tumefaciens strain LBA4404. Transformed EC were exposed to 400 mg l-1 2-deoxyglucose (2-DOG) as the selection agent. 2-DOG resistant tissues were regenerated into whole plantlets on various regeneration media containing the same concentration of 2-DOG. The plantlets were later transferred into soil and grown in a biosafety screenhouse. PCR and subsequently Southern blot analyses were carried out to confirm the integration of the transgene in the plantlets. A transformation efficiency of about 1.0% was obtained using DOGR1 gene into the genome of oil palm. This result demonstrates the potential of using combination of DOGR1 gene and 2-DOG for regenerating transgenic oil palm. PMID:26442041

  12. Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics.

    Science.gov (United States)

    Pietzke, Matthias; Zasada, Christin; Mudrich, Susann; Kempa, Stefan

    2014-01-01

    Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. Here, we describe pulsed stable isotope-resolved metabolomics (pSIRM) as a tool for the dynamic metabolic characterization of cellular metabolism. We have adapted gas chromatography-coupled mass spectrometric methods for metabolomic profiling and stable isotope-resolved metabolomics. In addition, we have improved robustness and reproducibility and implemented a strategy for the absolute quantification of metabolites. By way of examples, we have applied this methodology to characterize central carbon metabolism of a panel of cancer cell lines and to determine the mode of metabolic inhibition of glycolytic inhibitors in times ranging from minutes to hours. Using pSIRM, we observed that 2-deoxyglucose is a metabolic inhibitor, but does not directly act on the glycolytic cascade.

  13. Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake

    International Nuclear Information System (INIS)

    Wijns, W.; Melin, J.A.; Leners, N.

    1988-01-01

    Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism

  14. Whole body 18F-deoxyglucose positron emission tomography in detecting the primary focus of metastatic cancer with an unknown primary

    International Nuclear Information System (INIS)

    Chen Yingrui; Li Weixiong; Gu Meixin; Zhan Zhiguang; Zeng Zijun

    2002-01-01

    Objective: To evaluate the value of 18 F-deoxyglucose (FDG) positron emission tomography (PET) in detecting the primary focus of metastatic cancer with an unknown primary. Methods: Twenty-nine patients with various histological types of metastases from an unknown primary after extensive conventional diagnostic work-up were studied. After intravenous 370 MBq FDG, whole body scan was made 50 minutes after injection. The results of FDG PET were compared with those of CT or MRI. Results: With FDG PET, the primary tumors were identified in 13 patients and confirmed by pathology. The corresponding detection rate was 44.8% (13/29) as compared with 27.6% (8/29) by CT or MRI. In addition, 26 metastases were discovered by FDG PET whole body imaging but only 13 were found by CT or MRI. During 2-13 months' follow-up, the mortality rates were 15.4%(2/13) and 42.9%(6/14) for patients with the primary tumor identified or unidentified. Conclusions: FDG PET is valuable in staging, selecting appropriate treatment protocol and predicting prognosis for patients suffering from metastatic cancers with an unknown primary

  15. Effects of reinforcement-blocking doses of pimozide on neural systems driven by rewarding stimulation of the MFB: a /sup 14/C-2-deoxyglucose analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gomita, Y.; Gallistel, C.R.

    1982-10-01

    An analysis by means of /sup 14/C-2-deoxyglucose autoradiography of the neural systems unilaterally activated by the reinforcing stimulation used in the two accompanying papers revealed strong and reliable effects in the nucleus of the diagonal band of Broca, in the medial forebrain bundle (MFB) and/or the fornix throughout the diencephalon, and in the part of the anterior ventral tegmentum where the dopaminergic projection to the lateral habenula originates. The terminal fields of the dopaminergic forebrain projections were not affected, but there was bilateral suppression of lateral habenular activity. A second experiment found that the same systems are still activated by (automatically administered) reinforcing stimulation in rats treated with reinforcement blocking doses of pimozide. The only clear effect of pimozide was to reverse the bilateral suppressive effect of the stimulation on lateral habenular activity. Animals treated with pimozide show greatly elevated activity in the lateral habenula, whether or not they receive reinforcing stimulation. The results suggest that pimozide's effect on reinforcement is mediated by the circuitry interconnecting the lateral habenula with the nucleus of the diagonal band of Broca and/or the anterior ventral tegmentum.

  16. The influence of CA 125 and CEA levels on the results of {sup 18}F-deoxyglucose positron emission tomography in suspected recurrence of epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, C.; Gruenwald, F. [Johann Wolfgang Goethe University, Frankfurt/Main (Germany). Department of Nuclear Medicine; Doebert, N.; Hamscho, N.; Zaplatnikov, K.; Vasvatekis, S.; Matic, V.; Woerdehoff, N.

    2004-08-01

    Background and Purpose: The follow-up of epithelial ovarian cancer (OCA) consists of clinical investigation, sonography, and tumor markers (TMs), especially CA 125. If tumor recurrence is suspected, other imaging modalities including positron emission tomography (PET) with {sup 18}F-deoxyglucose (FDG) are often used. While there is still no consensus about the method of choice and the timing of its application, this study aims to find a TM threshold at which a PET would be appropriate. Material and Methods: A total of 90 PET studies and the associated CA 125 values (normal value <35 U/ml) were available in 71 patients during the follow-up afte primary therapy for OCA. In 48 studies a CEA value (normal value <3 ng/ml) was also available. The results of PET imaging were related to the level of TM increase. Results: In 23/90 studies the PET scan was normal. These patients had a median CA 125 of 13.3 U/ml (range 4.2-168 U/ml). In 67/90 studies the PET indicated a potential recurrence of OCA and the median CA 125 was 166.7 U/ml (range 13.3-4,060 U/ml). The TM levels were significantly different (p<0.001, U-test). With one exception, there were no normal PET scans above CA 125 levels of 30 U/ml; between 20 and 30 U/ml PET was positive in 4/7 studies. Conclusion: In suspected recurrence of OCA, if imaging modalities are to be used, an FDG PET may be considered. Since the costs of this investigation are high, it should be restricted to clinical situations where it is likely to be most effective. In this study a PET indication is worthwhile at CA 125 levels of approximately 30 U/ml. (orig.)

  17. [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography after limb salvage surgery: post-surgical appearance, attenuation correction and local complications

    Energy Technology Data Exchange (ETDEWEB)

    Gelfand, Michael J.; Sharp, Susan E. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Nuclear Medicine Division, Cincinnati, OH (United States)

    2015-08-15

    Metal endoprostheses and internal fixation devices cause significant artifacts on CT after limb salvage surgery; positron emission tomography (PET) images should be evaluated for artifacts. (1) To describe [F-18]2-fluoro-2-deoxyglucose (FDG) PET uptake patterns after limb salvage surgery. (2) To determine whether metal endoprostheses and fixation hardware cause significant artifacts on CT attenuation-corrected PET that interfere with diagnostic use of PET/CT after limb salvage surgery. We reviewed 92 studies from 18 patients ages 5-21 years. Diagnoses were osteogenic sarcoma in 14, Ewing sarcoma in 3, and malignant peripheral nerve sheath tumor originating in bone in 1. Nine patients had distal femur/knee endoprostheses, five had lower-extremity bone allografts secured by large metal plates and four had upper-extremity limb salvage procedures. Maximum standardized uptake value was calculated at lower-extremity soft-tissue-endoprosthesis interfaces. In 15 patients with PET/CT imaging, the first PET/CT scan after limb salvage surgery was reviewed for metal artifacts on CT images and for artifacts at locations on PET corresponding to the CT metal artifacts. Increased FDG uptake was consistently present at soft-tissue interfaces with endoprostheses, allografts and internal fixation devices, with little or no FDG uptake at cemented endoprosthesis-bone interfaces. Maximum standardized uptake value at margins of femur/knee endoprostheses ranged from 1.4 to 5.7. In four patients with distal femur/knee endoprostheses, minimal artifact was noted on attenuation-corrected PET images, but image interpretation was not affected. In the other 11 patients who had CT attenuation correction, we detected no artifacts caused by the attenuation correction. CT attenuation correction did not cause artifacts that affected interpretation of attenuation-corrected PET images. (orig.)

  18. Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic screening individuals.

    Science.gov (United States)

    Sekiguchi, Masau; Kakugawa, Yasuo; Terauchi, Takashi; Matsumoto, Minori; Saito, Hiroshi; Muramatsu, Yukio; Saito, Yutaka; Matsuda, Takahisa

    2016-12-01

    The sensitivity of 2-[ 18 F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is not yet fully understood. The present study aimed to clarify the sensitivity by analyzing large-scale data from an asymptomatic screening population. A total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy at our Cancer Screening Division between February 2004 and March 2013 were analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each examination was interpreted in a blinded fashion. The results of the two examinations were compared for each of the divided six colonic segments, with those from colonoscopy being set as the reference. The relationships between the sensitivity of FDG-PET and clinicopathological features of advanced neoplasms were also evaluated. Two hundred ninety-one advanced neoplasms, including 24 invasive cancers, were detected in 262 individuals. Thirteen advanced neoplasms (advanced adenomas) were excluded from the analysis because of the coexistence of lesions in the same colonic segment. The sensitivity, specificity, and positive and negative predictive values of FDG-PET for advanced neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 % CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %), respectively. The sensitivity was lower for lesions with less advanced histological grade, of smaller size, and flat-type morphology, and for those located in the proximal part of the colon. FDG-PET is believed to be difficult to use as a primary screening tool in population-based colorectal cancer screening because of its low sensitivity for advanced neoplasms. Even when it is used in opportunistic cancer screening, the limit of its sensitivity should be considered.

  19. Specific accumulation of 18F-deoxyglucose in three-dimensional long-term cultures of human and rodent brain tissue

    International Nuclear Information System (INIS)

    Hocke, C.; Prante, O.; Kuwert, T.; Bluemcke, I.; Jeske, I.; Romstoeck, J.; Stefan, H.

    2007-01-01

    Aim: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of 18 F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. Methods: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm 2 . Results: In rat hippocampal slices, FDG accumulated with 1 300 000 ± 68 000 counts/mm 2 , whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 ± 370 000 counts/mm 2 . The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. Conclusions: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo. (orig.)

  20. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2–Signal Transducer and Activator of Transcription 3 Pathway

    Directory of Open Access Journals (Sweden)

    Kai Hu

    2018-03-01

    Full Text Available Inflammation is an energy-intensive process, and caloric restriction (CR could provide anti-inflammatory benefits. CR mimetics (CRM, such as the glycolytic inhibitor 2-deoxyglucose (2-DG, mimic the beneficial effects of CR without inducing CR-related physiologic disturbance. This study investigated the potential anti-inflammatory benefits of 2-DG and the underlying mechanisms in mice with lipopolysaccharide (LPS-induced lethal endotoxemia. The results indicated that pretreatment with 2-DG suppressed LPS-induced elevation of tumor necrosis factor alpha and interleukin 6. It also suppressed the upregulation of myeloperoxidase, attenuated Evans blue leakage, alleviated histological abnormalities in the lung, and improved the survival of LPS-challenged mice. Treatment with 2-DG had no obvious effects on the total level of pyruvate kinase M2 (PKM2, but it significantly suppressed LPS-induced elevation of PKM2 in the nuclei. Prevention of PKM2 nuclear accumulation by ML265 mimicked the anti-inflammatory benefits of 2-DG. In addition, treatment with 2-DG or ML265 suppressed the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3. Inhibition of STAT3 by stattic suppressed LPS-induced inflammatory injury. Interestingly, posttreatment with 2-DG at the early stage post-LPS challenge also improved the survival of the experimental animals. This study found that treatment with 2-DG, a representative CRM, provided anti-inflammatory benefits in lethal inflammation. The underlying mechanisms included suppressed nuclear PKM2-STAT3 pathway. These data suggest that 2-DG might have potential value in the early intervention of lethal inflammation.

  1. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2-Signal Transducer and Activator of Transcription 3 Pathway.

    Science.gov (United States)

    Hu, Kai; Yang, Yongqiang; Lin, Ling; Ai, Qing; Dai, Jie; Fan, Kerui; Ge, Pu; Jiang, Rong; Wan, Jingyuan; Zhang, Li

    2018-01-01

    Inflammation is an energy-intensive process, and caloric restriction (CR) could provide anti-inflammatory benefits. CR mimetics (CRM), such as the glycolytic inhibitor 2-deoxyglucose (2-DG), mimic the beneficial effects of CR without inducing CR-related physiologic disturbance. This study investigated the potential anti-inflammatory benefits of 2-DG and the underlying mechanisms in mice with lipopolysaccharide (LPS)-induced lethal endotoxemia. The results indicated that pretreatment with 2-DG suppressed LPS-induced elevation of tumor necrosis factor alpha and interleukin 6. It also suppressed the upregulation of myeloperoxidase, attenuated Evans blue leakage, alleviated histological abnormalities in the lung, and improved the survival of LPS-challenged mice. Treatment with 2-DG had no obvious effects on the total level of pyruvate kinase M2 (PKM2), but it significantly suppressed LPS-induced elevation of PKM2 in the nuclei. Prevention of PKM2 nuclear accumulation by ML265 mimicked the anti-inflammatory benefits of 2-DG. In addition, treatment with 2-DG or ML265 suppressed the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 by stattic suppressed LPS-induced inflammatory injury. Interestingly, posttreatment with 2-DG at the early stage post-LPS challenge also improved the survival of the experimental animals. This study found that treatment with 2-DG, a representative CRM, provided anti-inflammatory benefits in lethal inflammation. The underlying mechanisms included suppressed nuclear PKM2-STAT3 pathway. These data suggest that 2-DG might have potential value in the early intervention of lethal inflammation.

  2. [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography after limb salvage surgery: post-surgical appearance, attenuation correction and local complications

    International Nuclear Information System (INIS)

    Gelfand, Michael J.; Sharp, Susan E.

    2015-01-01

    Metal endoprostheses and internal fixation devices cause significant artifacts on CT after limb salvage surgery; positron emission tomography (PET) images should be evaluated for artifacts. (1) To describe [F-18]2-fluoro-2-deoxyglucose (FDG) PET uptake patterns after limb salvage surgery. (2) To determine whether metal endoprostheses and fixation hardware cause significant artifacts on CT attenuation-corrected PET that interfere with diagnostic use of PET/CT after limb salvage surgery. We reviewed 92 studies from 18 patients ages 5-21 years. Diagnoses were osteogenic sarcoma in 14, Ewing sarcoma in 3, and malignant peripheral nerve sheath tumor originating in bone in 1. Nine patients had distal femur/knee endoprostheses, five had lower-extremity bone allografts secured by large metal plates and four had upper-extremity limb salvage procedures. Maximum standardized uptake value was calculated at lower-extremity soft-tissue-endoprosthesis interfaces. In 15 patients with PET/CT imaging, the first PET/CT scan after limb salvage surgery was reviewed for metal artifacts on CT images and for artifacts at locations on PET corresponding to the CT metal artifacts. Increased FDG uptake was consistently present at soft-tissue interfaces with endoprostheses, allografts and internal fixation devices, with little or no FDG uptake at cemented endoprosthesis-bone interfaces. Maximum standardized uptake value at margins of femur/knee endoprostheses ranged from 1.4 to 5.7. In four patients with distal femur/knee endoprostheses, minimal artifact was noted on attenuation-corrected PET images, but image interpretation was not affected. In the other 11 patients who had CT attenuation correction, we detected no artifacts caused by the attenuation correction. CT attenuation correction did not cause artifacts that affected interpretation of attenuation-corrected PET images. (orig.)

  3. The influence of CA 125 and CEA levels on the results of 18F-deoxyglucose positron emission tomography in suspected recurrence of epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Menzel, C.; Gruenwald, F.; Doebert, N.; Hamscho, N.; Zaplatnikov, K.; Vasvatekis, S.; Matic, V.; Woerdehoff, N.

    2004-01-01

    Background and Purpose: The follow-up of epithelial ovarian cancer (OCA) consists of clinical investigation, sonography, and tumor markers (TMs), especially CA 125. If tumor recurrence is suspected, other imaging modalities including positron emission tomography (PET) with 18 F-deoxyglucose (FDG) are often used. While there is still no consensus about the method of choice and the timing of its application, this study aims to find a TM threshold at which a PET would be appropriate. Material and Methods: A total of 90 PET studies and the associated CA 125 values (normal value <35 U/ml) were available in 71 patients during the follow-up afte primary therapy for OCA. In 48 studies a CEA value (normal value <3 ng/ml) was also available. The results of PET imaging were related to the level of TM increase. Results: In 23/90 studies the PET scan was normal. These patients had a median CA 125 of 13.3 U/ml (range 4.2-168 U/ml). In 67/90 studies the PET indicated a potential recurrence of OCA and the median CA 125 was 166.7 U/ml (range 13.3-4,060 U/ml). The TM levels were significantly different (p<0.001, U-test). With one exception, there were no normal PET scans above CA 125 levels of 30 U/ml; between 20 and 30 U/ml PET was positive in 4/7 studies. Conclusion: In suspected recurrence of OCA, if imaging modalities are to be used, an FDG PET may be considered. Since the costs of this investigation are high, it should be restricted to clinical situations where it is likely to be most effective. In this study a PET indication is worthwhile at CA 125 levels of approximately 30 U/ml. (orig.)

  4. Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P: a 19F NMR spectroscopy study in the rat.

    Science.gov (United States)

    Southworth, Richard; Parry, Craig R; Parkes, Harold G; Medina, Rodolfo A; Garlick, Pamela B

    2003-12-01

    2-Fluoro-[(18)F]-2-deoxy-glucose (FDG) is a positron-emitting analogue of glucose used clinically in positron emission tomography (PET) to assess glucose utilization in diseased and healthy tissue. Originally developed to measure local cerebral glucose utilization rates, it has now found applications in tumour diagnosis and in the study of myocardial glucose uptake. Once taken up into the cell, FDG is phosphorylated to FDG-6-phosphate (FDG-6-P) by hexokinase and was originally believed to be trapped as a terminal metabolite. This 'metabolic trapping' of FDG-6-P forms the basis of the analysis of PET data. In this study, we have used (19)F NMR spectroscopy to investigate FDG metabolism following the injection of a bolus of the glucose tracer into the rat (n=6). Ninety minutes after the (19)FDG injection, the brain, heart, liver and kidneys were removed and the (19)FDG metabolites in each were extracted and quantified. We report that significant metabolism of FDG occurs beyond FDG-6-P in all organs examined and that the extent of this metabolism varies from tissue to tissue (degree of metabolism beyond FDG-6-P, expressed as percentage of total organ FDG content, was brain 45 +/- 3%; heart 29 +/- 2%; liver 22+/-3% and kidney 17 +/- 3%, mean +/- SEM n=6). Furthermore, we demonstrate that the relative accumulation of each metabolite was tissue-dependent and reflected the metabolic and regulatory characteristics of each organ. Such inter-tissue differences may have implications for the mathematical modelling of glucose uptake and phosphorylation using FDG as a glucose tracer. Copyright 2003 John Wiley & Sons, Ltd.

  5. Determination of Glucose Utilization Rates in Cultured Astrocytes and Neurons with [14C]deoxyglucose: Progress, Pitfalls, and Discovery of Intracellular Glucose Compartmentation.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F; Sokoloff, Louis; Driscoll, Bernard F

    2017-01-01

    2-Deoxy-D-[ 14 C]glucose ([ 14 C]DG) is commonly used to determine local glucose utilization rates (CMR glc ) in living brain and to estimate CMR glc in cultured brain cells as rates of [ 14 C]DG phosphorylation. Phosphorylation rates of [ 14 C]DG and its metabolizable fluorescent analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), however, do not take into account differences in the kinetics of transport and metabolism of [ 14 C]DG or 2-NBDG and glucose in neuronal and astrocytic cells in cultures or in single cells in brain tissue, and conclusions drawn from these data may, therefore, not be correct. As a first step toward the goal of quantitative determination of CMR glc in astrocytes and neurons in cultures, the steady-state intracellular-to-extracellular concentration ratios (distribution spaces) for glucose and [ 14 C]DG were determined in cultured striatal neurons and astrocytes as functions of extracellular glucose concentration. Unexpectedly, the glucose distribution spaces rose during extreme hypoglycemia, exceeding 1.0 in astrocytes, whereas the [ 14 C]DG distribution space fell at the lowest glucose levels. Calculated CMR glc was greatly overestimated in hypoglycemic and normoglycemic cells because the intracellular glucose concentrations were too high. Determination of the distribution space for [ 14 C]glucose revealed compartmentation of intracellular glucose in astrocytes, and probably, also in neurons. A smaller metabolic pool is readily accessible to hexokinase and communicates with extracellular glucose, whereas the larger pool is sequestered from hexokinase activity. A new experimental approach using double-labeled assays with DG and glucose is suggested to avoid the limitations imposed by glucose compartmentation on metabolic assays.

  6. Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane

    International Nuclear Information System (INIS)

    Sanfeliu, C.; Sola, C.; Camon, L.; Martinez, E.; Rodriguez-Farre, E.

    1990-01-01

    Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures. Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication

  7. 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury genetic algorithm

    International Nuclear Information System (INIS)

    Rodrigues, Rosana S.; Bozza, Fernando A.; Hanrahan, Christopher J.; Wang, Li-Ming; Wu, Qi; Hoffman, John M.; Zimmerman, Guy A.; Morton, Kathryn A.

    2017-01-01

    Introduction: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Methods: Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 h following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results: Significant uptake of 18 F-FDG occurred by 2 h following LPS, and progressively increased to 24 h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14

  8. 2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP) by increasing O-GlcNAcylation – Implications for targeting the Warburg effect in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Shin Yee; Hagen, Thilo, E-mail: bchth@nus.edu.sg

    2015-10-02

    The high proliferation rate of cancer cells and the microenvironment in the tumor tissue require the reprogramming of tumor cell metabolism. The major mechanism of metabolic reprogramming in cancer cells is the Warburg effect, defined as the preferential utilization of glucose via glycolysis even in the presence of oxygen. Targeting the Warburg effect is considered as a promising therapeutic strategy in cancer therapy. In this regard, the glycolytic inhibitor 2-deoxyglucose (2DG) has been evaluated clinically. 2DG exerts its effect by directly inhibiting glycolysis at the level of hexokinase and phosphoglucoisomerase. In addition, 2DG is also known to induce the expression of thioredoxin interacting protein (TXNIP), a tumor suppressor protein and an important negative regulator of cellular glucose uptake. Hence, characterization of the mechanism through which 2DG regulates TXNIP expression may reveal novel approaches to target the Warburg effect in cancer cells. Therefore, in this study we sought to test various hypotheses for the mechanistic basis of the 2DG dependent TXNIP regulation. We have shown that 2DG induced TXNIP expression is independent of carbohydrate response element mediated transcription. Furthermore, the induction of TXNIP is neither dependent on the ability of 2DG to deplete cellular ATP nor to cause endoplasmic reticulum stress. We found that the 2DG induced TXNIP expression is at least in part dependent on the inhibition of the O-GlcNAcase enzyme and the accumulation of O-GlcNAc modified proteins. These results have implications for the identification of therapeutic targets to increase TXNIP expression in cancer. - Highlights: • 2DG increases TXNIP expression at the mRNA and protein level. • The effect of 2DG on TXNIP is independent of ChoRE mediated transcription. • 2DG induces TXNIP independent of ER stress induction and ATP depletion. • 2DG inhibits OGA and leads to accumulation of O-GlcNAcylated proteins. • The upregulation of

  9. Effect of duration of fasting and diet on the myocardial uptake of F-18-2-fluoro-2-deoxyglucose (F-18 FDG) at rest

    International Nuclear Information System (INIS)

    Kumar, Pankaj; Patel, Chetan D; Singla, Suhas; Malhotra, A

    2014-01-01

    Patterns of myocardial fluoro-2-deoxyglucose (FDG) uptake with respect to duration of fasting and dietary modifications. We observed the effect of duration of fasting and diet on the myocardial uptake pattern of F-18 FDG in patients routinely referred for oncological evaluation and no previous history of Coronary Artery Disease (CAD). Prospective study. A total of 153 patients (M: 81, F: 72; mean age: 47 ± 15 years; mean blood glucose level (mBG) 105 ± 23 mg/dl) were randomly divided in three groups. Group A: 4-6 h fasting; Group B: Overnight fasting (12–14 h); Group C: Low carbohydrate and fat rich diet for 2 days coupled with overnight fasting prior to the positron emission tomography (PET) scan. FDG uptake was classified as following: 1) homogeneous uptake, 2) heterogeneous uptake, and 3) ‘no uptake’ in the left ventricular (LV) myocardium. FDG PET study was performed as standard protocol for oncological conditions. Descriptive statistics, Chi-square test or Fisher's exact test, and Spearman's rank correlation tests were applied. We observed the ‘no uptake’ pattern in five (10%), 28 (55%), and 39 (77%), ‘heterogeneous’ pattern in 20 (39%), 14 (28%), and seven (14%), and ‘homogeneous’ pattern in 26 (51%), nine (18%), and five (10%) patients in Group A, B, and C, respectively. There was statistically significant difference of myocardial uptake pattern between group A and B (P < 0.0001), between group A and C (P < 0.0001), and between Group B and C (P = 0.023). The mBG was 102, 105, and 111 mg/dl in ‘no uptake’, heterogeneous, and homogeneous uptake pattern, respectively, (P = 0.103). Also, within each group the mBG was not related to the uptake pattern. Both restricted diet and duration of fasting play an important role in determining the pattern and suppression of myocardial F-18 FDG uptake. Overnight fasting and restricted diet together suppress myocardial FDG uptake more than overnight fasting alone, which suppresses uptake

  10. Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors; Utilidad del estudio PET con FDG en la evaluacion de sarcomas de diverso origen y de tumores no sarcoma-no epiteliales

    Energy Technology Data Exchange (ETDEWEB)

    Massardo, Teresa [Seccion Medicina Nuclear, Departamento de Medicina, Hospital Clinico Universidad de Chile, Santiago (Chile); Jofre, Maria Josefina; Sierralta, Maria Paulina; Canessa, Jose [Centro PET de imagenes moleculares, Hospital Militar de Santiago, Santiago (Chile); Castro, Gabriel; Berrocal, Isabel [Seccion Medicina Nuclear, Departamento de Medicina, Hospital Clinico Universidad de Chile, Santiago (Chile); Gallegos, Ivan [Departamento Anatomia Patologica, Hospital Clinico Universidad de Chile, Santiago (Chile)

    2012-07-01

    Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. Results: FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. Conclusions: PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

  11. Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I and II) non-small cell lung cancers (NSCLC)

    International Nuclear Information System (INIS)

    Agarwal, Mohit; Brahmanday, Govinda; Bajaj, Sunil K.; Wong, Ching-Yee Oliver; Ravikrishnan, K.P.

    2010-01-01

    The aims were to determine if the maximum standardized uptake value (SUV max ) of the primary tumor as determined by preoperative 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging. A retrospective clinicopathologic review of 363 patients who had a preoperative 18 F-FDG PET done before undergoing attempted curative resection for early-stage (I and II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUV max yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUV max and optimal cutoff SUV max were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUV max 's independency of other prognostic factors for the prediction of overall survival. The median duration of follow-up was 981 days (2.7 years). The median SUV max was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUV max was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUV max [i.e., each log (base 2) unit increase in SUV max ] was associated with a 1.28-fold [95% confidence interval (CI): 1.03-1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUV max when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively

  12. Kinetics of high-Level of ß-glucosidase production by a 2-deoxyglucose-resistant mutant of Humicola lanuginosa in submerged fermentation Cinética de produção de ß-glucosidase por um mutante de Hemicola lanuginosa resistente a 2-deoxiglucose em fermentação submersa

    Directory of Open Access Journals (Sweden)

    Syed Ali Imran Bokhari

    2008-12-01

    Full Text Available A 2-deoxyglucose-resistant mutant (M7 of Humicola lanuginosa was obtained by exposing conidia to γ-rays and permitting expression in broth containing 0.6% 2-deoxyglucose (DG and cellobiose (1% before plating on DG esculin-ferric ammonium citrate agar medium from which colonies showing faster and bigger blackening zones were selected. Kinetic parameters for enhanced ß-glucosidase (BGL synthesis by M7 were achieved when corncobs acted as the carbon source. The combination between corncobs and corn steep liquor was the best to support higher values of all product formation kinetic parameters. Effect of temperature on the kinetic and thermodynamic attributes of BGL production equilibrium in the wild organismand M7was studied using batch process at eight different temperatures in shake-flask studies. The best performance was found at 45ºC and 20 g L-1 corncobs in 64 h. Both growth and product formation (17.93 U mL-1 were remarkably high at 45ºC and both were coupled under optimum working conditions. Product yield of BGL from the mutant M7 (1556.5 U g-1 dry corncobs was significantly higher than the values reported on all fungal and bacterial systems. Mutation had thermo-stabilization influence on the organism and mutant required lower activation energy for growth and lower magnitudes of enthalpy and entropy for product formation than those demanded by the wild organism, other mesophilic and thermo-tolerant organisms. In the inactivation phase, the organisms needed lower values of activation energy, enthalpy and entropy for product formation equilibrium, confirming thermophilic nature of metabolic network possessed by the mutant organism.Um mutante de Hemicola lanuginosa resistente a 2-deoxiglucose(M7 foi obtido através de exposição de conídios a raios γ, permitindo a expressão em caldo contendo 0,6% de 2-deoxiglucose (DG e celobiose (1% antes da semeadura em ágar DG esculina citrato de ferro amoniacal, da qual foram selecionadas as col

  13. 2-Deoxyglucose autoradiography of single motor units: labelling of individual acutely active muscle fibers

    International Nuclear Information System (INIS)

    Toop, J.; Burke, R.E.; Dum, R.P.; O'Donovan, M.J.; Smith, C.B.

    1982-01-01

    2-Deoxy-D-[1- 14 C]glucose (2DG) was given intravenously during repetitive stimulation of single motor units in adult cats and autoradiographs were made of frozen sections of the target muscles in order to evaluate methods designed to improve the spatial resolution of [ 14 C]2DG autoradiography. With the modifications used, acutely active muscle fibers, independently identified by depletion of intrafiber glycogen, were associated with highly localized accumulations of silver grains over the depleted fibers. The results indicate that [ 14 C]2DG autoradiography can successfully identify individual active muscle fibers and might in principle be used to obtain quantitative data about rates of glucose metabolism in single muscle fibers of defined histochemical type. The modifications may be applicable also to other tissues to give improved spatial resolution with [ 14 C]-labeled metabolic markers. (Auth.)

  14. Fluoro-2-deoxy-glucose positron emission tomography in oncology: are we there yet?

    International Nuclear Information System (INIS)

    Khafagi, F.A.

    2001-01-01

    Evaluating the clinical utility of diagnostic imaging technologies, beyond the relatively straightforward assessment of diagnostic utility (sensitivity, specificity, predictive accuracy), is difficult, because a number of possible management steps are interposed between the diagnostic procedure and the final patient outcome. Nevertheless, the application of FDG PET to oncological patients has been examined more carefully than most other diagnostic imaging modalities. As a result of such evaluations, the US Health Care Financing Administration (HCFA) has approved reimbursement for FDG PET for the following indications: evaluation of indeterminate solitary pulmonary nodules, initial staging of lung cancer, detection of recurrent colorectal cancer with rising carcinoembryonic antigen levels, detection of recurrent malignant melanoma and staging and re staging of Hodgkin's disease and non-Hodgkin's lymphoma

  15. Basic principles of 18F-fluoro-deoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Standke, R.

    2002-01-01

    Positron emission tomography uses photons to receive regional information about dynamic, physiologic, and biochemical processes in the living body. A positron decay is measured indirectly by the simultaneous registration of both gamma rays created by the annihilation. The event is counted, if two directly opposite located detectors register gamma rays in coincidence. Unfortunately the detectors of a positron emission tomography system do not register only true coincident events. There are also scattered and random coincidences. Different types of positron tomographs are presented and scintillation crystals, which are in use for positron emission tomography are discussed. The 2D- and 3D-acquisition methods are described as well as preprocessing methods, such as correction for attenuation, scatter and dead time. For quantification the relative parameter standard uptake value (SUV) is explained. Finally hybrid systems, such as combined positron emission tomography/computed tomography scanners and the use of computed tomography data for attenuation correction are introduced. (author)

  16. Comparison of cancer glucose utilization indexes by positron emission tomography using fluorine-18-fluoro-deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Kyosan (Chiba Univ. (Japan). School of Medicine)

    1994-08-01

    Positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) has been used to diagnose various kinds of malignant tumors. Various indexes are calculated for evaluation of tumor glucose metabolism from FDG PET image. Some indexes need sequential multiple-time uptake data and arterial plasma FDG concentrations (dynamic study). But some indexes use only static image data to calculate. We calculated four kinds of indexes on each patient, and analyzed the correlation of each index with others. Previously untreated 35 patients (23 non-Hodgikin's lymphoma, 4 lung cancers, 2 epipharynx cancers and other 6 malignant tumors) were studied by FDG PET. In all patients, about 4 mCi (148 MBq) of FDG was injected intravenously in a fasting state, and a series of 2-min sequential scans was acquired for 60 min following injection. After sequential scans, 6-min scan was successively added for obtaining static image. The rate constants (k[sub 1]-k[sub 4]) calculated by non-linear least squares fitting routines, the slope of Patlak-Gjedde plot, differential absorption ratio (DAR) which represents tumor activity corrected by administrated dose per body weight, and tumor-to-normal soft-tissue contrast ratios (TCR) were calculated for each patient. The correlation of these indexes was analyzed statistically. Patlak-Gjedde plot seemed to be widely accepted for measuring tumor glucose metabolism, but it needs dynamic study data. DAR is a simple index easily calculated using static data. Our results showed that the slope of Patlak-Gjedde plot and DAR were closely correlated. It was suggested that the DAR could be used in place of Patlak-Gjedde plot. They also showed relatively well correlation with each other. Correlation between rate constant k[sub 3] and other indexes were from 0.67 to 0.43. It is acceptable result because rate constant K[sub 3] related the activity of hexokinase but other indexes may represent the overall glucose metabolism of the tumor tissue. (J.N.P.).

  17. High-resolution 2-deoxyglucose mapping of functional cortical columns in mouse barrel cortex.

    Science.gov (United States)

    McCasland, J S; Woolsey, T A

    1988-12-22

    Cortical columns associated with barrels in layer IV of the somatosensory cortex were characterized by high-resolution 2-deoxy-D-glucose (2DG) autoradiography in freely behaving mice. The method demonstrates a more exact match between columnar labeling and cytoarchitectonic barrel boundaries than previously reported. The pattern of cortical activation seen with stimulation of a single whisker (third whisker in the middle row of large hairs--C3) was compared with the patterns from two control conditions--normal animals with all whiskers present ("positive control")--and with all large whiskers clipped ("negative control"). Two types of measurements were made from 2DG autoradiograms of tangential cortical sections: 1) labeled cells were identified by eye and tabulated with a computer, and 2) grain densities were obtained automatically with a computer-controlled microscope and image processor. We studied the fine-grained patterns of 2DG labeling in a nine-barrel grid with the C3 barrel in the center. From the analysis we draw five major conclusions. 1. Approximately 30-40% of the total number of neurons in the C3 barrel column are activated when only the C3 whisker is stimulated. This is about twice the number of neurons labeled in the C3 column when all whiskers are stimulated and about ten times the number of neurons labeled when all large whiskers are clipped. 2. There is evidence for a vertical functional organization within a barrel-related whisker column which has smaller dimensions in the tangential direction than a barrel. There are densely labeled patches within a barrel which are unique to an individual cortex. The same patchy pattern is found in the appropriate regions of sections above and below the barrels through the full thickness of the cortex. This functional arrangement could be considered to be a "minicolumn" or more likely a group of "minicolumns" (Mountcastle: In G.M. Edelman and U.B. Mountcastle (eds): The Material Brain: Cortical Organization and the Group-Selective Theory of Higher Brain Function. Cambridge: MIT Press, '78). 3. Within the stereotyped geometry of the barrel field, there is considerable individual variation in the radial labeling distribution in corresponding (homotypical) columns of different cerebral hemispheres. This result is consistent with the hypothesis that dynamic processes operate to determine the connection strengths between neural elements in somatosensory cortex. It provides a basis for testing various "connectionist" and "group selection" theories of neural organization and development.(ABSTRACT TRUNCATED AT 400 WORDS)

  18. Mapping of functional activity in brain with 18F-fluoro-deoxyglucose

    International Nuclear Information System (INIS)

    Alavi, A.; Reivich, M.; Greenberg, J.; Wolf, A.

    1981-01-01

    A model has been designed based on the assumptions of a steady state for glucose consumption, a first-order equilibration of the free 14 C-DG pool in the tissue with the plasma level, and relative rates of phosphorylation of 14 C-DG and glucose determined by their kinetic constants for hexokinase reaction. Using an operational equation based on this model, the metabolic rates of glucose are calculated in various regions of brain (utilizing brain slices and autoradiography). 14 C is a beta emitter and therefore not suitable for noninvasive imaging in man. With the synthesis of 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-DG) all of the requirements for a suitable radiopharmaceutical for the determination of local cerebral metabolism have been met. This agent behaves very similarly to 14 C-DG and therefore, using the above described model and emission tomography, it has become possible to measure regional cerebral metabolism for the first time in man

  19. Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography

    International Nuclear Information System (INIS)

    Brudin, L.H.; Valind, S.O.; Rhodes, C.G.; Pantin, C.F.; Sweatman, M.; Jones, T.; Hughes, J.M.B.

    1994-01-01

    Regional pulmonary glucose metabolism (MR glu ; μmol h -1 g -1 ), extravascular lung density (D EV ; g cm -3 ) and vascular volume (V B ; ml cm -3 ) were measured in a single midthoracic transaxial slice (-2 cm thick) using positron emission tomography (PET) in seven patients with histologically proven sarcoidosis. The measurements were repeated 1-7 months later after steroid therapy (in two cases, no treatment) in order to assess MR glu as an index of inflammation and relate it to routine pulmonary function tests, chest radiography and serum angiotensin converting enzyme (SACE) levels. MR glu was computed from serial lung scans and peripheral venous blood samples for 60 min following an i.v. injection of 18 F-2-fluoro-2-deoxy-D-glucose ( 18 FDG). Both MR glu (which was increased in six of seven patients) and elevated SACE levels returned to normal in those patients treated with high-dose steroids. Regional vascular volume was normal in six of seven cases and did not change significantly with therapy. The high tissue density measured in all patients decreased significantly in two of three patients treated with 40 mg prednisolone daily. The abnormal MR glu observed in active sarcoidosis becomes normal pari passu with SACE levels during high-dose steroid therapy. We conclude that MR glu measured with 18 FDG and PET may reflect ''disease activity'' in sarcoidosis in quantitative terms (per gram lung tissue) and in respect of disease distribution. (orig.)

  20. Characteristics of (3H)2-Deoxyglucose Uptake by Slices of Rat Cerebral Cortex

    Science.gov (United States)

    1983-05-17

    changes occur (Quastel, 1969). Unlike in liver and in kidney, there is no appreciable gluconeogenesis from pyruvate or from lactate in brain...Bachelard 1976). When the neuronal activity of whole brain in vivo is increased by electrical stimulation, metabolic changes occur including...respiration can increase up to 10 times their resting rates (Bachelard, 1970). These are examples of the close association between neuronal ac- tivity and

  1. Phosphorylation and 14-3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose

    DEFF Research Database (Denmark)

    Harthill, Jean E; Meek, Sarah E M; Morrice, Nick

    2006-01-01

    Trehalose-6-phosphate is a 'sugar signal' that regulates plant metabolism and development. The Arabidopsis genome encodes trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphatase (TPP) enzymes. It also encodes class II proteins (TPS isoforms 5-11) that contain both TPS-like and TPP...

  2. Apparent discrepancy between single-unit activity and [14C]deoxyglucose labeling in optic tectum of the rattlesnake

    International Nuclear Information System (INIS)

    Auker, C.R.; Meszler, R.M.; Carpenter, D.O.

    1983-01-01

    Autoradiographic analysis of [1- 14 C]2-deoxy-D-glucose-6-phosphate ([ 14 C]2-DG-P) accumulation in the rattlesnake brain stem and optic tectum was used in an effort to map infrared and visual neuronal pathways. Visual stimulation with a standard stimulus (a heat lamp) resulted in dense labeling of the superficial layers of the optic tectum. Infrared stimulation resulted in labeling at the first synaptic relay, the lateral descending nucleus of the trigeminal tract, but not at higher levels. Responses of infrared units in one hemitectum and visual units in the other were analyzed. There were no clear differences in the number, maximal density, spread, or rates of accommodation of visual units and infrared units, although the locus of maximal density was more superficial for visual units. In general, infrared units generated a greater number of action potentials. All infrared units responded to onset but they varied greatly in their ability to maintain discharge for the duration of the stimulus. Infrared stimuli generated single, large, triphasic on-responses, whereas visual stimulation generated complex multiphasic and long-lasting on- and off-responses. The major infrared-on peak reached maximal amplitude at greater depths and was larger than the major visual-on peak. Amplitude of the infrared peak fell off more rapidly with distance than did amplitude of the visual peak. These observations are consistent with the view that infrared stimulation is effective in discharging neurons but is not associated with intense synaptic excitation. Our observations suggest that 2-deoxy-D-glucose uptake is not necessarily correlated with the degree of action potential activation of specific neuronal pathways. The amount of [ 14 C]2-DG-P labeling may reflect the metabolic requirements for support of synaptic depolarization as well as that supporting action potentials

  3. Use of F-18 fluoro deoxyglucose (FDG) positron emission tomography (PET) in the assessment of malignant mesothelioma

    International Nuclear Information System (INIS)

    Brown, F.M.M.; Pathmaraj, K.; Berlangieri, S.U.; Knight, S.; Clarke, C.P.; Scott, A.M.

    2002-01-01

    Full text: Australia has the highest mesothelioma incidence rate in the world and the incidence of Mesothelioma is increasing. Therapy for Mesothelioma involves surgery (including phototherapy), radiotherapy and chemotherapy. Computed tomography (CT) is frequently used to stage the extent of Mesothelioma. This study aimed to evaluate the utility of FDG PET in staging Mesothelioma and monitoring response to therapy. Nineteen F-18 FDG PET was performed at the A and RMC Centre for PET in 14 patients (13M: 1F, age range 39-77 years, mean age 58 years) with biopsy proven malignant pleural Mesothelioma. Patients were referred for staging (5 patients) or evaluation of patients post surgery or phototherapy (9 patients). 3 patients had more than 1 PET scan. FDG scans were reviewed with full access to the CT report. Standardised Uptake Values (SUV) were performed in all scans in regions of maximal FDG uptake corresponding to CT abnormality. Normal lung SUVs were also calculated. Follow-up was possible in all patients to the time of death or December 2001 (Follow-up 4 - 45 months, mean 16 months; 3 patients still alive). All FDG PET scans were positive for FDG-avid pleural tissue. No surgery was deferred due to FDG PET findings. In 3 patients mediastinal nodes were identified pre-surgery. Post surgical therapy assessment by FDG PET (9 patients) guided therapy by confirming disease progression or further characterising post-operative changes when CT findings were uncertain. FDG PET was able to more accurately distinguish between collapse/consolidation and recurrent disease than CT scan. Almost all post-surgical scans were performed in patients who received phototherapy. Different Mesothelioma histological subtypes could not be differentiated by SUV criteria. False positive FDG PET studies were seen in 3 patients, all of whom had post-surgical empyemas. In conclusion, FDG PET has a potential role in the management of malignant mesothelioma patients, particularly in the post-therapy assessment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  4. Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose

    International Nuclear Information System (INIS)

    Gambhir, S.S.; Schwaiger, M.; Huang, S.C.; Krivokapich, J.; Schelbert, H.R.; Nienaber, C.A.; Phelps, M.E.

    1989-01-01

    To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate

  5. Differential [14C]2-deoxyglucose uptake after deafferentation of the mammalian auditory pathway - a model for examining tinnitus

    International Nuclear Information System (INIS)

    Sasaki, C.T.; Kauer, J.S.; Babitz, L.

    1980-01-01

    The authors have used 2-DG in examining metabolic changes of the auditory pathways after surgical deafferentation, consequences of which within a week or so often produce the pathophysiological condition of tinnitus in humans. The findings identify increased glucose uptake related to increased neuronal activity after chronic cochlear ablation and may thus represent an analog of the tinnitus phenomenon in man. (Auth.)

  6. Differential (/sup 14/C)2-deoxyglucose uptake after deafferentation of the mammalian auditory pathway - a model for examining tinnitus

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, C T; Kauer, J S; Babitz, L [Yale Univ., New Haven, CT (USA). School of Medicine

    1980-08-04

    The authors have used 2-DG in examining metabolic changes of the auditory pathways after surgical deafferentation, consequences of which within a week or so often produce the pathophysiological condition of tinnitus in humans. The findings identify increased glucose uptake related to increased neuronal activity after chronic cochlear ablation and may thus represent an analog of the tinnitus phenomenon in man.

  7. Glucose metabolism-weighted imaging with chemical exchange-sensitive MRI of 2-deoxyglucose (2DG) in brain: Sensitivity and biological sources.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2016-12-01

    Recent proof-of-principle studies have demonstrated the feasibility of measuring the uptake and metabolism of non-labeled 2-deoxy-D-glucose (2DG) by a chemical exchange-sensitive spin-lock (CESL) MRI approach. In order to gain better understanding of this new approach, we performed dynamic in vivo CESL MRI on healthy rat brains with an intravenous injection of 2DG under various conditions at 9.4T. For three 2DG doses of 0.25, 0.5 and 1g/kg, we found that 2DG-CESL signals increased linearly with injection dose at the initial (40min) suggesting time-dependent differential weightings of 2DG transport and metabolism. Remaining 2DG-CESL studies were performed with 0.25g/kg 2DG. Since a higher isoflurane level reduces glucose metabolism and increases blood flow, 2DG-CESL was measured under 0.5%, 1.5% and 2.2% isoflurane. The 2DG-CESL signal was reduced at higher isoflurane levels correlating well with the 2DG phosphorylation in the intracellular space. To detect regional heterogeneities of glucose metabolism, 2DG-CESL with 0.33×0.33×1.50mm 3 resolution was obtained, which indeed showed a higher response in the cortex compared to the corpus callosum. Lastly, unlike CESL MRI with the injection of non-transportable mannitol, the 2DG-CESL response decreased with an increased spin-lock pulse power confirming that 2DG-CESL is dominated by chemical exchange processes in the extravascular space. Taken together, our results showed that 2DG-CESL MRI signals mainly indicate glucose transport and metabolism and may be a useful biomarker for metabolic studies of normal and diseased brains. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The usefulness of integrated PET/CT simulator for non-small cell lung cancer using the F-18 fluoro-2-deoxyglucose (FDG)

    Energy Technology Data Exchange (ETDEWEB)

    Na, Jong Eok; Suh, Jeong Nam; Kim, Jin Soo; Kim, Dae Seob; Hong, Dong Ki; Baek, Geum Mun [Dept. of Radiation Oncology, Asan Medical Center, Seoul (Korea, Republic of)

    2013-03-15

    To evaluate the usefulness of Integrated PET/CT and compare the gloss tumor volume (GTV) identified on CT, PET, PET/CT to that obtained from fluorodeoxyglucose (FDG). This experimental study was obtained using GE Discovery 690 (General Electric Healthcare, Milwaukee, MI, USA) PET/CT simulator with Gammex Laser System for five non-small cell lung cancer (NSCLC) patients. In order to increase the reproducibility of the patient setup, We have to fixed to patients using the Extended Wing Board. GTV delineation was painted using the EclipseTM ver.10 contouring program for CT, PET, PET/CT images. And then, We were to compare the changes in the GTV. These results are drawn from 5 patients who have atelectasis or pneumonitis. Compared to CT defined GTV, PET was decreased by 10.5%, 11.8% and increased by 67.9%, 220%, 19.4%. PET/CT was decreased by 7.7%, 6.7%, 28% and increased by 232%, 24%. We were able to determine the usefulness of PET/CT simulator for NSCLC. PET/CT simulator in radiation therapy is useful to define the target volume and It is possible to delineate Objective and accurate target volume. It seems to be applicable to other areas in the near future.

  9. Regional glucose hypometabolic spread within the primary motor cortex is associated with amyotrophic lateral sclerosis disease progression: A fluoro-deoxyglucose positron emission tomography study

    Directory of Open Access Journals (Sweden)

    Hironobu Endo

    2017-03-01

    Conclusions: In patients with ALS, glucose metabolism decreased in the impaired side of the primary motor cortex depending on the clinical symptom progression in the corresponding extremities, regardless of the presence of clinical UMN signs. A decrement in glucose metabolism on FDG-PET corresponding to symptoms in the primary motor cortex might be an indicator of the time-dependent course of ALS neurodegeneration.

  10. Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Ishida, Jiro; Abe, Yoshiyuki; Mochizuki, Hidetaka; Tsuda, Hitoshi; Asakawa, Hideki; Omata, Jiro; Fukatsu, Kazuhiko; Kondo, Nobuo; Kondo, Tadaharu; Hama, Yukihiro; Tamura, Katsumi

    2008-01-01

    Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose ( 18 F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18 F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC). One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18 F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18 F-FDG PET/CT, we studied both a visual assessment of 18 F-FDG uptake and standardized uptake value (SUV) for axillary staging. In a visual assessment of 18 F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18 F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18 F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18 F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18 F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18 F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03). The diagnostic accuracy of 18 F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18 F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18 F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis

  11. Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

    2009-01-01

    CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

  12. Neural input is critical for arcuate hypothalamic neurons to mount intracellular signaling responses to systemic insulin and deoxyglucose challenges in male rats: implications for communication within feeding and metabolic control networks.

    Science.gov (United States)

    Khan, Arshad M; Walker, Ellen M; Dominguez, Nicole; Watts, Alan G

    2014-02-01

    The hypothalamic arcuate nucleus (ARH) controls rat feeding behavior in part through peptidergic neurons projecting to the hypothalamic paraventricular nucleus (PVH). Hindbrain catecholaminergic (CA) neurons innervate both the PVH and ARH, and ablation of CA afferents to PVH neuroendocrine neurons prevents them from mounting cellular responses to systemic metabolic challenges such as insulin or 2-deoxy-d-glucose (2-DG). Here, we asked whether ablating CA afferents also limits their ARH responses to the same challenges or alters ARH connectivity with the PVH. We examined ARH neurons for three features: (1) CA afferents, visualized by dopamine-β-hydroxylase (DBH)- immunoreactivity; (2) activation by systemic metabolic challenge, as measured by increased numbers of neurons immunoreactive (ir) for phosphorylated ERK1/2 (pERK1/2); and (3) density of PVH-targeted axons immunoreactive for the feeding control peptides Agouti-related peptide and α-melanocyte-stimulating hormone (αMSH). Loss of PVH DBH immunoreactivity resulted in concomitant ARH reductions of DBH-ir and pERK1/2-ir neurons in the medial ARH, where AgRP neurons are enriched. In contrast, pERK1/2 immunoreactivity after systemic metabolic challenge was absent in αMSH-ir ARH neurons. Yet surprisingly, axonal αMSH immunoreactivity in the PVH was markedly increased in CA-ablated animals. These results indicate that (1) intrinsic ARH activity is insufficient to recruit pERK1/2-ir ARH neurons during systemic metabolic challenges (rather, hindbrain-originating CA neurons are required); and (2) rats may compensate for a loss of CA innervation to the ARH and PVH by increased expression of αMSH. These findings highlight the existence of a hierarchical dependence for ARH responses to neural and humoral signals that influence feeding behavior and metabolism.

  13. Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT in combination with ultrasonography for axillary staging in primary breast cancer

    Directory of Open Access Journals (Sweden)

    Tamura Katsumi

    2008-06-01

    Full Text Available Abstract Background Accurate evaluation of axillary lymph node (ALN involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT and axillary ultrasonography (AUS for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB and preoperative systemic chemotherapy (PSC. Methods One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND. Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV for axillary staging. Results In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12 in 18F-FDG PET uptake only, 80% (4 of 5 in AUS positive only, and 100% (28 of 28 in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03. Conclusion The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis.

  14. In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

    Science.gov (United States)

    Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

    2017-02-01

    Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (pbladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

  15. In situ formation of the amino sugars 1-amino-1-deoxy-fructose and 2-amino-2-deoxy-glucose under Maillard reaction conditions in the absence of ammonia.

    Science.gov (United States)

    Nashalian, Ossanna; Yaylayan, Varoujan A

    2016-04-15

    Replacing amino acids with their binary metal complexes during the Maillard reaction can initiate various processes, including the oxidative degradation of their glucose conjugates, generating 1-amino-1-deoxy-fructose and its derivatives. These reactive amino sugars are not easily accessible under Maillard reaction conditions and are only formed in the presence of ammonia. To explore the generality of this observation and to study in particular the ability of fructose to generate glucosamine, the amino acid-metal complexes were heated in aqueous solutions with three aldohexoses and two ketohexoses at 110°C for 2 h and the dry residues were analysed by ESI/qTOF/MS/MS. All the sugars generated relatively intense ions at [M+H](+) 180 (C6H14NO5); those ions originating from ketohexoses exhibited MS/MS fragmentations identical to glucosamine and those originating form aldohexoses showed ions identical to fructosamine. Furthermore, the amino sugars were found to form fructosazine, react with other sugars and undergo dehydration reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Tissue distributions of radiopharmaceuticals labeled with positron emitters and problems in relating them to human studies

    International Nuclear Information System (INIS)

    Christman, D.R.

    1980-01-01

    This paper discusses a few specific examples of organ distributions involving positron-emitting nuclides intended to illustrate some specific points in this area. In particular, work with 2-fluoro-2-deoxyglucose will be discussed in some detail, and its distribution in the body compared with the closely related (chemically but not biologically) 3-fluoro-3-deoxyglucose and 1- 11 C-2-deoxyglucose. Other compounds labeled with these two nuclides, and with 13 N and 15 O will also be discussed

  17. Positron imaging studies

    International Nuclear Information System (INIS)

    Budinger, T.F.; Ganz, E.; Moyer, B.R.; Yano, Y.; Mathis, C.A.; Friedland, R.P.

    1982-01-01

    Several methods for the noninvasive evaluation of the metabolism and blood perfusion of brain and heart are reviewed. Heart muscle perfusion can be followed by measuring the accumulation of rubidium-82 simultaneously with the measurement of the arterial input. Deoxyglucose labelled with fluorine-18 was used to study the role of insulin in deoxyglucose accumulation

  18. Rôle de la tomographie par émission de positrons avec le 18-fluoro-deoxyglucose (PET-FDG) dans la détection précoce d'une non-stérilisation tumorale des carcinomes bucco-pharyngo-laryngés

    OpenAIRE

    Haenggeli, C A; Dulguerov, Pavel; Slosman, Daniel; Becker, Minerva; Bang, Pascal Ilhyun; Allal, Abdelkarim Said; Guyot, J P; Lehmann, Willy

    2000-01-01

    To evaluate and compare the performances of FDG-PET imaging, MRI and clinical examination in the detection of residual tumour 3 months after treatment of patients with head and neck squamous cell carcinoma.

  19. Local cerebral glucose utilization in the beagle puppy model of intraventricular hemorrhage

    International Nuclear Information System (INIS)

    Ment, L.R.; Stewart, W.B.; Duncan, C.C.

    1982-01-01

    Local cerebral glucose utilization has been measured by means of carbon-14( 14 C)-autoradiography with 2-deoxyglucose in the newborn beagle puppy model of intraventricular hemorrhage. Our studies demonstrate gray matter/white matter differentiation of uptake of 14 C-2-deoxyglucose in the control pups, as would be expected from adult animal studies. However, there is a marked homogeneity of 14 C-2-deoxyglucose uptake in all brain regions in the puppies with intraventricular hemorrhage, possibly indicating a loss of the known coupling between cerebral blood flow and metabolism in this neuropathological condition

  20. Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders

    National Research Council Canada - National Science Library

    Brown, Susan

    1999-01-01

    ... (HE) and familial amyotrophic lateral sclerosis (FALS), using transgenic mouse models. Studies in this first year employed C-14-2-deoxyglucose in vivo autoradiography and spectrophotometric metabolic enzyme assays...

  1. Metabolic neural mapping in neonatal rats

    International Nuclear Information System (INIS)

    DiRocco, R.J.; Hall, W.G.

    1981-01-01

    Functional neural mapping by 14 C-deoxyglucose autoradiography in adult rats has shown that increases in neural metabolic rate that are coupled to increased neurophysiological activity are more evident in axon terminals and dendrites than neuron cell bodies. Regions containing architectonically well-defined concentrations of terminals and dendrites (neuropil) have high metabolic rates when the neuropil is physiologically active. In neonatal rats, however, we find that regions containing well-defined groupings of neuron cell bodies have high metabolic rates in 14 C-deoxyglucose autoradiograms. The striking difference between the morphological appearance of 14 C-deoxyglucose autoradiograms obtained from neonatal and adult rats is probably related to developmental changes in morphometric features of differentiating neurons, as well as associated changes in type and locus of neural work performed

  2. Sympathetic ingrowth: A result of cholinergic nerve injury in the adult mammalian brain

    International Nuclear Information System (INIS)

    Davis, J.N.

    1986-01-01

    This paper describes sympathetic ingrowth, its regulation and function. The study leads to a better understanding of the molecular mechanisms that probably underlie the regulation of other neuronal rearrangements. The authors examine tritium-2-deoxyglucose uptake in the hippocampal formation after septal leasions. Preliminary experiments suggest that the septo-hippocampal fibers do influence tritium-2-deoxyglucose uptake throughout the hippocampal formation in normal animals. If sympathetic ingrowth also can influence this uptake, this could provide further evidence for an adaptive role of this noradrenergic replacement of cholinergic neurons

  3. Effects of β₂-agonists on force during and following anoxia in rat extensor digitorum longus muscle

    DEFF Research Database (Denmark)

    Fredsted, A; Gissel, H; Ortenblad, N

    2012-01-01

    of salbutamol on force recovery were prevented by blocking the Na(+),K(+)- pumps with ouabain or by blocking glycolysis with 2-deoxyglucose. Dibutyryl cAMP (1 mM) or theophylline (1 mM) also improved force recovery remarkably. In anoxic muscles, salbutamol decreased intracellular Na(+), increased (86)Rb uptake...

  4. Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects

    DEFF Research Database (Denmark)

    Lund, Jenny; S Tangen, Daniel; Wiig, Håvard

    2018-01-01

    deoxyglucose accumulation and fractional glucose oxidation (glucose oxidation relative to glucose uptake), and were also more sensitive to the suppressive action of acutely added oleic acid to the cells. Despite lack of correlation of fibre types between skeletal muscle biopsies and cultured cells, myotubes...

  5. PET-imaging of cerebral glucose metabolism during sleep and dreaming

    International Nuclear Information System (INIS)

    Heiss, W.D.; Pawlik, G.; Herholz, K.; Wagner, R.; Wienhard, K.

    1985-01-01

    Positron emission tomography (PET) of ( 18 F)-2-fluoro-2-deoxyglucose (FDG) affording non-invasive repeatable quantification of local cerebral glucose utilization was employed to determine possible differential effects of sleep, with and without dreaming, on regional brain metabolism of normal volunteers also measured during wakefulness. (author). 7 refs.; 1 tab

  6. Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

    DEFF Research Database (Denmark)

    Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars

    2013-01-01

    and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data. RESULTS: PA increased glucose uptake by approximately 35...

  7. Elucidation and modulation of glucocorticoid-induced apoptosis in acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Eberhart, K.

    2011-01-01

    This thesis deals with the elucidation of the synergistic effect of the glucocorticoid dexamethasone and the metabolic modulator 2-deoxyglucose on apoptosis induction in two in vitro model systems of childhood acute lymphoblastic leukemia. 2-deoxyglucose accelerated the kinetics of, and increased the sensitivity to, glucocorticoid-induced apoptosis in two leukemia cell lines. In primary lymphocytes from healthy donors, in contrast, 2-deoxyglucose and dexamethasone did not act synergistically on apoptosis induction. To elucidate the molecular basis of the synergistic effect, glycolysis by means of glucose uptake, lactate production, ATP levels, glucose transporter and hexokinase expression and mitochondrial oxygen consumption was analyzed in treated vs. untreated cells. The study revealed a downregulation of gene expression of the glucose transporter GLUT1 and hexokinase 2 (HK2), release of HK2 from the outer mitochondrial membrane, as well as reduced glycolysis and mitochondrial respiration. Moreover, the analysis of the mitochondrial proteome by 2 dimensional differential gel electrophoresis after treatment with 2-deoxyglucose and dexamethasone revealed the regulation of several interesting candidate proteins involved in treatment related apoptosis. (author)

  8. Isolation of a Kluyveromyces fragilis derepressed mutant hyperproducer of inulinase for ethanol production from Jerusalem artichoke

    Energy Technology Data Exchange (ETDEWEB)

    Bourgi, J.; Guirand, J.P.; Galzy, P.

    1986-01-01

    A paritally derepressed mutant of Kluyveromyces fragilis showing hyperproduction of inulinase was isolated by means of ethylmethanesulfonate mutation followed by a 2-deoxyglucose selection. This mutant is suitable for the fermentation of inulin and Jerusalem artichoke extracts containing large amounts of inulin high polyfructosans type (early extracts).

  9. Rac1 governs exercise-stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

    DEFF Research Database (Denmark)

    Sylow, Lykke; Laurent, Ida; Kleinert, Maximilian

    2016-01-01

    is a candidate molecule. This study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise-induced uptake of radiolabelled 2-deoxyglucose (2-DG) at 65% max running capacity was blocked in soleus and decreased by 80 and 60...

  10. MR imaging and positron emission tomography of cortical heterotopia

    Energy Technology Data Exchange (ETDEWEB)

    Bairamian, D.; Di Chiro, G.; Theodore, W.H.; Holmes, M.D.; Dorwart, R.H.; Larson, S.M.

    1985-11-01

    Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using YF-2-deoxyglucose.

  11. MR imaging and positron emission tomography of cortical heterotopia

    International Nuclear Information System (INIS)

    Bairamian, D.; Di Chiro, G.; Theodore, W.H.; Holmes, M.D.; Dorwart, R.H.; Larson, S.M.

    1985-01-01

    Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18 F-2-deoxyglucose

  12. Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

    International Nuclear Information System (INIS)

    Jacobson, L.

    1989-01-01

    There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain [ 14 C]-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain [ 14 C]-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO 2 correlated with the severity of hypoxia at arterial PCO 2 below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O 2

  13. Huntington's disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia

    2011-01-01

    In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...

  14. Synthesis of no-carrier-added fluorine-18 2-fluoro-2-deoxy-d-glucose

    International Nuclear Information System (INIS)

    Tewson, T.J.

    1983-01-01

    A new synthetic procedure for the preparation of fluorine-18 2-fluoro-2-deoxy-glucose has been developed. This procedure offers the advantages of flexibility in the source of the fluorine-18, high yields, and short synthesis times. The procedure works at the no-carrier-added level and gives a product of very high specific activity

  15. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  16. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...... artery (MCAO) in rats. In halothane anesthesia, the left middle cerebral artery was permanently occluded. Two hours after MCAO an i.v. bolus injection of 14C-deoxyglucose and 3H-leucine was given and circulated for 45 min. Two sets of brain sections were processed for quantitative autoradiography....... Neighboring brain sections exposed an X-ray film (3H-insensitive), and a 3H-sensitive for determination of rCMRglc and PS, respectively. Sections for PS determination were washed in trichloroacetic acid (TCA) prior to film exposure in order to remove 14C-deoxyglucose and unincorporated 3H-leucine. Regional...

  17. Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

    Science.gov (United States)

    Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

    2015-04-09

    Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

  18. Metabolic Hyperactivity of the Medial Posterior Parietal Lobes in Psychogenic Tremor

    Directory of Open Access Journals (Sweden)

    Peter Hedera

    2012-05-01

    Full Text Available Background: The pathophysiology of psychogenic movement disorders, including psychogenic tremor (PT, is only emerging. Case Report: This is a single case report of a patient who met diagnostic criteria for PT. He underwent positron emission tomography (PET of brain with 18F-deoxyglucose at resting state. His PET study showed symmetrically increased 18F-deoxyglucose uptake in both posterior medial parietal lobes. There was no corresponding abnormality on structural imaging. Discussion: Hypermetabolism of the medial aspects of posterior parietal lobes bilaterally may reflect abnormal activity of sensory integration that is important in the pathogenesis of PT. This further supports the idea that non-organic movement disorders may be associated with detectable functional brain abnormalities.

  19. Amino acid residues involved in ligand preference of the Snf3 transporter-like sensor in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Dietvorst, J.; Karhumaa, Kaisa; Kielland-Brandt, Morten

    2010-01-01

    /preferences of Snf3. The ability of cells to sense sugars in vivo was monitored by following the degradation of the Mth1 protein, :ill earl., event ill the signal pathway. Our study reveals that Snf3. ill addition to glucose. also senses fructose and mannose, as well as the glucose analogues 2-deoxyglucose, 3-O......-methylglucoside and 6-deoxyglucose. The signalling proficiency of a non-phosphorylatable analogue strongly supports the notion that sensing through Snf3 does not require sugar phosphorylation. Sequence comparisons of Snf3 to glucose transporters indicated amino acid residues possibly involved in sensing of sugars other...... than glucose. By site-specific mutagenesis of the structural gene, roles of specific residues in Snf3 could he established. Change of isoleucine-374 to valine ill transmembrane segment 7 of Snf3 partially abolished sensing of fructose mannose. while mutagenesis causing it change of phenylalanine-462 (4...

  20. Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

    Science.gov (United States)

    Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

    2018-01-01

    Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

  1. Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

    DEFF Research Database (Denmark)

    Johansen, Torben

    1981-01-01

    The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior...... to initiation of the release process by the antigen-antibody reaction. The secretory capacity of mast cells was less related to the cellular level of ATP at the time of activation of the release process by the antigen-antibody reaction than to the rate of cellular energy supply. Furthermore, mast cells were...... pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should...

  2. Isolation and Characterization of a Catabolite Repression-Insensitive Mutant of a Methanol Yeast, Candida boidinii A5, Producing Alcohol Oxidase in Glucose-Containing Medium

    OpenAIRE

    Sakai, Yasuyoshi; Sawai, Tohru; Tani, Yoshiki

    1987-01-01

    Mutants exhibiting alcohol oxidase (EC 1.1.3.13) activity when grown on glucose in the presence of methanol were found among 2-deoxyglucose-resistant mutants derived from a methanol yeast, Candida boidinii A5. One of these mutants, strain ADU-15, showed the highest alcohol oxidase activity in glucose-containing medium. The growth characteristics and also the induction and degradation of alcohol oxidase were compared with the parent strain and mutant strain ADU-15. In the parent strain, initia...

  3. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

    International Nuclear Information System (INIS)

    Schwartz, W.J.

    1987-01-01

    In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the 14 C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia

  4. Enzymatic Biosynthesis of Novel Resveratrol Glucoside and Glycoside Derivatives

    OpenAIRE

    Pandey, Ramesh Prasad; Parajuli, Prakash; Shin, Ju Yong; Lee, Jisun; Lee, Seul; Hong, Young-Soo; Park, Yong Il; Kim, Joong Su; Sohng, Jae Kyung

    2014-01-01

    A UDP glucosyltransferase from Bacillus licheniformis was overexpressed, purified, and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugar-conjugated resveratrol glycosides. Significantly higher (90%) bioconversion of resveratrol was achieved with α-d-glucose as the sugar donor to produce four different glucosides of resveratrol: resveratrol 3-O-β-d-glucoside, resveratrol 4′-O-β-d-glucoside, resveratr...

  5. Utilidad del estudio PET con FDG en la evaluación de sarcomas de diverso origen y de tumores no sarcoma-no epiteliales

    OpenAIRE

    Massardo,Teresa; Jofré,María Josefina; Sierralta,María Paulina; Canessa,José; Castro,Gabriel; Berrocal,Isabel; Gallegos,Iván

    2012-01-01

    Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sa...

  6. Digital imaging of regional glucose metabolism of the heart with a MWPC

    International Nuclear Information System (INIS)

    Bellazzini, R.; Camici, P.; Coppini, G.; Del Guerra, A.; Massai, M.M.; Ragadini, M.; Spandre, G.; Tonelli, G.

    1983-01-01

    The digital imaging of carbohydrate consumption in myocardial tissue has been performed by using a deposit tracer of glucose metabolism ( 3 H-deoxyglucose) and a specially designed Multiwire Proportional Chamber (MWPC) that acts as a position sensitive radioactivity detector. The resolving power (approx. =1.5 mm FWHM), sensitivity (approx. =10 -1 Bq/cm 2 ), efficiency (approx. =10%) and uniformity (+ or -4%) of the system are shown and MWPC digital autoradiographs of canine heart in different pathophysiological conditions are presented

  7. Rare solitary focal tuberculous involvement of liver masquerading as hepatic metastasis on FDG PET/CT in a case of fibular round cell tumor

    International Nuclear Information System (INIS)

    Puranik, Ameya D; Purandare, Nilendu C; Sridhar, Epari; Agrawal, Archi; Shah, Sneha; Rangarajan, Venkatesh

    2015-01-01

    Finding of focal 18F-fluoro-deoxyglucose (FDG) uptake in liver on FDG positron emission tomography/computed tomography (FDG PET/CT) in a known case of malignancy is often considered to be metastases. We report a similar finding on FDG PET/CT in a case of Ewing's sarcoma of thigh, which turned out to be of tuberculous etiology, an unusual cause of false positive FDG uptake in the liver

  8. 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation

    OpenAIRE

    Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

    2017-01-01

    Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all i...

  9. Positron emission tomography. Basic principles

    International Nuclear Information System (INIS)

    Rodriguez, Jose Luis; Massardo, Teresa; Gonzalez, Patricio

    2001-01-01

    The basic principles of positron emission tomography (PET) technique are reviewed. lt allows to obtain functional images from gamma rays produced by annihilation of a positron, a positive beta particle. This paper analyzes positron emitters production in a cyclotron, its general mechanisms, and the various detection systems. The most important clinical applications are also mentioned, related to oncological uses of fluor-l8-deoxyglucose

  10. Nuclear medicine and imaging research. Quantitative studies in radiopharmaceutical science. Comprehensive progress report, January 1, 1983-June 30, 1985

    International Nuclear Information System (INIS)

    Beck, R.N.; Cooper, M.D.

    1985-09-01

    This comprehensive report outlines the progress made during the past three years in the areas described below. In all instances, initial studies have been carried out and the technical feasibility of carrying through each study has been demonstrated. The studies described include development of cesium-130 and bromine-75 radioisotope generators, the feasibility of using rubidium-82 as a myocardial imaging agent, and radiochemical preparation of C-11 deoxyglucose. 28 refs. (DT)

  11. Spasticity complicating metrizamide myelography

    Energy Technology Data Exchange (ETDEWEB)

    Earl, H M; Earl, C J; Kendall, B E

    1985-09-01

    Temporary but considerable increase in spasticity following myelography using metrizamide at 300 mgsI/ml concentration occurred in 4 patients. In 3 of the patients the diagnosis is uncertain, but it is likely to be some form of degenerative disease involving motor pathways in two of them; the fourth case has cervical spondylotic myelopathy. The spasticity might be related to the anticholinesterase activity of metrizamide or to competative inhibition by the deoxyglucose component of the metrizamide molecule of endogenous glucose metabolism.

  12. Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Garlick, P.B.; Medina, R.A.; Southworth, R.; Marsden, P.K. [Department of Radiological Sciences, Guy' s, King' s and St. Thomas' School of Medicine, London (United Kingdom)

    1999-10-01

    Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart. (orig.)

  13. Heterogeneous response of isolated adult rat heart cells to insulin

    International Nuclear Information System (INIS)

    Haworth, R.A.; Hunter, D.R.; Berkoff, H.A.

    1984-01-01

    3-O-Methylglucose uptake by Ca2+-resistant adult rat heart cells in suspension was measured, free of artifactual inhibitor-insensitive uptake, and with an accuracy of +/- 1.9% pellet water. (Ca2+-resistant cells are cells which retain their original rod-shaped morphology in the presence of physiological levels of Ca2+.) High levels of insulin (10(-6) M) stimulated the rate of 3-O-methylglucose uptake approximately 10-fold. In the presence of low levels of insulin (3 X 10(-11) M, 10(-10) M) uptake was biphasic; it could not be described by a single exponential function within experimental error, but required the sum of two exponentials. Deviation from a single exponential function was not so great with high levels of insulin (10(-6) M) or no insulin. Cell sugar uptake was also investigated using autoradiography of cells which had accumulated [2-14C]deoxyglucose under similar conditions. This showed considerable heterogeneity of 2-deoxyglucose uptake by cells treated with low levels of insulin, but significantly less heterogeneity of 2-deoxyglucose uptake by cells treated with high levels of insulin. It is concluded that the deviation of 3-O-methylglucose uptake from a single exponential observed at low insulin levels can be accounted for in terms of a heterogeneous response of cells to insulin

  14. Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart

    International Nuclear Information System (INIS)

    Garlick, P.B.; Medina, R.A.; Southworth, R.; Marsden, P.K.

    1999-01-01

    Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart. (orig.)

  15. Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

    Science.gov (United States)

    Mathai, Michael L; Soueid, Mona; Chen, Nora; Jayasooriya, Anura P; Sinclair, Andrew J; Wlodek, Mary E; Weisinger, Harrison S; Weisinger, Richard S

    2004-11-01

    To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking beta-oxidation of fatty acids (by beta-mercaptoacetate injection). DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to beta-mercaptoacetate. These findings indicate that supply of omega-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of omega-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

  16. Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

    Science.gov (United States)

    Poitry-Yamate, C.; Gianoncelli, A.; Kourousias, G.; Kaulich, B.; Lepore, M.; Gruetter, R.; Kiskinova, M.

    2013-10-01

    Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19F in 19FDG, trapped as intracellular 19F-deoxyglucose-6-phosphate (19FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19F-deoxyglucose-6P is structurally identical to 18F-deoxyglucose-6P, LEXRF of subcellular 19F provides a link to in vivo 18FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18FDG PET image, and the contribution of neurons and glia to the PET signal.

  17. Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

    International Nuclear Information System (INIS)

    Poitry-Yamate, C; Lepore, M; Gruetter, R; Gianoncelli, A; Kourousias, G; Kiskinova, M; Kaulich, B

    2013-01-01

    Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19 F in 19 FDG, trapped as intracellular 19 F-deoxyglucose-6-phosphate ( 19 FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19 FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19 FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19 F-deoxyglucose-6P is structurally identical to 18 F-deoxyglucose-6P, LEXRF of subcellular 19 F provides a link to in vivo 18 FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18 FDG PET image, and the contribution of neurons and glia to the PET signal

  18. The molecular architecture of QdtA, a sugar 3,4-ketoisomerase from Thermoanaerobacterium thermosaccharolyticum.

    Science.gov (United States)

    Thoden, James B; Holden, Hazel M

    2014-06-01

    Unusual di- and trideoxysugars are often found on the O-antigens of Gram-negative bacteria, on the S-layers of Gram-positive bacteria, and on various natural products. One such sugar is 3-acetamido-3,6-dideoxy-D-glucose. A key step in its biosynthesis, catalyzed by a 3,4-ketoisomerase, is the conversion of thymidine diphosphate (dTDP)-4-keto-6-deoxyglucose to dTDP-3-keto-6-deoxyglucose. Here we report an X-ray analysis of a 3,4-ketoisomerase from Thermoanaerobacterium thermosaccharolyticum. For this investigation, the wild-type enzyme, referred to as QdtA, was crystallized in the presence of dTDP and its structure solved to 2.0-Å resolution. The dimeric enzyme adopts a three-dimensional architecture that is characteristic for proteins belonging to the cupin superfamily. In order to trap the dTDP-4-keto-6-deoxyglucose substrate into the active site, a mutant protein, H51N, was subsequently constructed, and the structure of this protein in complex with the dTDP-sugar ligand was solved to 1.9-Å resolution. Taken together, the structures suggest that His 51 serves as a catalytic base, that Tyr 37 likely functions as a catalytic acid, and that His 53 provides a proton shuttle between the C-3' hydroxyl and the C-4' keto group of the hexose. This study reports the first three-dimensional structure of a 3,4-ketoisomerase in complex with its dTDP-sugar substrate and thus sheds new molecular insight into this fascinating class of enzymes. © 2014 The Protein Society.

  19. Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography

    International Nuclear Information System (INIS)

    Schwaiger, M.; Brunken, R.; Grover-McKay, M.; Krivokapich, J.; Child, J.; Tillisch, J.H.; Phelps, M.E.; Schelbert, H.R.

    1986-01-01

    Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Design of steady-state positron emission tomography protocols for neurobehavioral studies: CO15O and 19Ne

    International Nuclear Information System (INIS)

    Kearfott, K.J.; Rottenberg, D.A.; Volpe, B.T.

    1983-01-01

    Although the [ 18 F]-2-fluoro-2-deoxyglucose positron emission tomographic technique for measuring regional glucose metabolic rate has been successfully employed for neurobehavioral studies, the long (greater than 30 min) equilibration time required may complicate the interpretation of experimental results. Positron emission tomography neurobehavioral protocols employing the continuous inhalation of CO 15 O and 19 Ne were developed for measuring regional cerebral blood flow during multiple control and stimulation periods. Timing, lung absorbed dose, statistical accuracy, and resolution were considered. Studies with 19 Ne require shorter equilibration and stimulation times than do CO 15 O studies but entail higher absorbed doses and yield poorer imaging statistics

  1. Utility of FDG-PET in neuropediatric pathology; Utilidad del PET-FDG en patologia neuropediatrica

    Energy Technology Data Exchange (ETDEWEB)

    Massardo, Teresa V; Canessa G, Jose; Sierralta C, M. Paulina; Gonzalez E, Pstricio; Jofre M, M. Josefina [Centro PET Imagenes Moleculares Hospital Militar de Santiago (Chile)

    2007-07-01

    Due to the recent incorporation of positron technology (PET) it appears interesting to review the present indications of fluor-deoxyglucose (FDG) in neuropediatric pathology. The main indication is in the evaluation of refractory epilepsy mainly in cases with negative magnetic resonance or discordance with electroencephalography Some uses in tumors are also discussed, such as tumor characterization and differentiation between radionecrosis and recurrence. The experience between years 2003 and 2007 at the Santiago Military Hospital, using FDG in 66 children and adolescents cases with diverse neurological indications was reviewed.

  2. Usefulness of PET-FDG in pathology neuropediatric; Utilidad del PET-FDG en patologia neuropediatrica

    Energy Technology Data Exchange (ETDEWEB)

    Massardo V, Teresa; Canessa G, Jose; Sierralta C, M Paulina; Gonzalez E, Patricio; Jofre M, M Josefina [Centro PET Imagenes Moleculares Hospital Militar de Santiago, Santiago (Chile)

    2007-07-01

    Due to the recent incorporation of positron technology (PET) it appears interesting to review the present indications of fluor-deoxyglucose (FDG) in neuropediatric pathology. The main indication is in the evaluation of refractory epilepsy mainly in cases with negative magnetic resonance or discordance with electro encephalography Some uses in tumors are also discussed, such as tumor characterization and differentiation between radio necrosis and recurrence. The experience between years 2003 and 2007 at the Santiago Military Hospital, using FDG in 66 children and adolescents cases with diverse neurological indications was reviewed (au)

  3. Usefulness of PET-FDG in pathology neuropediatric

    International Nuclear Information System (INIS)

    Massardo V, Teresa; Canessa G, Jose; Sierralta C, M.Paulina; Gonzalez E, Patricio; Jofre M, M.Josefina

    2007-01-01

    Due to the recent incorporation of positron technology (PET) it appears interesting to review the present indications of fluor-deoxyglucose (FDG) in neuropediatric pathology. The main indication is in the evaluation of refractory epilepsy mainly in cases with negative magnetic resonance or discordance with electro encephalography Some uses in tumors are also discussed, such as tumor characterization and differentiation between radio necrosis and recurrence. The experience between years 2003 and 2007 at the Santiago Military Hospital, using FDG in 66 children and adolescents cases with diverse neurological indications was reviewed (au)

  4. A cell-based fluorescent glucose transporter assay for SGLT2 inhibitor discovery

    Directory of Open Access Journals (Sweden)

    Yi Huan

    2013-04-01

    Full Text Available The sodium/glucose cotransporter 2 (SGLT2 is responsible for the majority of glucose reabsorption in the kidney, and currently, SGLT2 inhibitors are considered as promising hypoglycemic agents for the treatment of type 2 diabetes mellitus. By constructing CHO cell lines that stably express the human SGLT2 transmembrane protein, along with a fluorescent glucose transporter assay that uses 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino]2-deoxyglucose (2-NBDG as a glucose analog, we have developed a nonradioactive, cell-based assay for the discovery and characterization of SGLT2 inhibitors.

  5. Duchenne muscular dystrophy: normal ATP turnover in cultured cells

    International Nuclear Information System (INIS)

    Fox, I.H.; Bertorini, T.; Palmieri, G.M.A.; Shefner, R.

    1986-01-01

    This paper examines ATP metabolism in cultured muscle cells and fibroblasts from patients with Duchenne dystrophy. ATP and ADP levels were the same in cultured cells from normal subjects and patients and there was no difference in ATP synthesis or degradation. The ATP synthesis was measured by the incorporation of C 14-U-adenine into aTP and ADP. although there was a significant decrease in radioactively labelled ATP after incubation with deoxyglucose in Duchenne muscle cells, there was no difference in ATP concentration of ADP metabolism

  6. Effects of a low-voltage static electric field on energy metabolism in astrocytes.

    Science.gov (United States)

    Huang, R; Peng, L; Hertz, L

    1997-01-01

    Mouse astrocytes (glial cells) in primary cultures were exposed to a low-voltage static DC electric field with no current flow and thus with no generation of magnetic fields. The electric field altered the rate of glycolysis, measured by 2-deoxyglucose accumulation. The magnitude and direction of this effect depended on the polarization of the field and the applied voltage. The maximum effect was an increase of approximately 30%, which occurred with field across the cells at an intensity that can be calculated to be 0.3 mV/cm or less. Reversal of the polarization converted the stimulation to a small but statistically significant inhibition.

  7. Functional imaging of the brain with18F-fluorodeoxyglucose

    International Nuclear Information System (INIS)

    Reivich, M.; Greenberg, J.; Alavi, A.; Hand, P.; Rintelmann, W.; Rosenquist, A.; Christman, D.; Fowler, J.; MacGregor, R.; Wolf, A.

    1980-01-01

    A techniques is reported by which it is possible to determine which regions of the human brain become functionally active in response to a specific stimulus. The method utilizes 18 F-2-fluoro-2-deoxyglucose ([ 18 F]-FDG) administered as a bolus. [ 18 F]-FDG is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation. The subject is then scanned during administration of a physiologic stimulus by position emission tomography and the three-dimensional distribution of 18 F activity in the brain determined

  8. A Consortium to Develop the Medical Uses of NMR Imaging, NMR Spectroscopy, and Positron Emission Tomography. Final report, 6/1/92 - 5/31/98

    International Nuclear Information System (INIS)

    Smith, Gary T.

    1998-01-01

    During years one, two and three, this project concentrated on quantifying skeletal muscle blood flow and metabolism for assessment of ischemia. The ultimate goal is to provide a non-invasive method of measuring viability of skeletal muscle following traumatic vascular compromise. The technique involves the use of both dynamic positron emission tomography (PET) coupled with compartmental model analysis of the resulting time activity relationships and nuclear magnetic resonance spectroscopy (NMRS). PET scanning is ideally suited for this project because of the capability to utilize labeled organic compounds. Blood flow was measured with N-13 ammonia. Metabolism was assessed with F-18 deoxyglucose (FDG)

  9. Cerebral glucose metabolism in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

    1984-02-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

  10. Concurrent Endometrial Carcinosarcoma and Thyroid Papillary Carcinoma: PET CT Imaging Findings

    Directory of Open Access Journals (Sweden)

    Mine Genc

    2015-06-01

    Full Text Available The aim of this study is to report a patient who was diagnosed with a concurrent primary tumor by 18-fluoro-2-deoxy-glucose positron emission tomography (FDG PET imaging performed for staging of an endometrial cancer. FDG uptake was detected in the uterus, where the primary cancer was located, and in the left lobe of the thyroid gland. The biopsy sample from the hypermetabolic nodular lesion in thyroid gland revealed intermediate cytology according to Bethesda Classification. The patient underwent hysterectomy and thyroidectomy. An endometrial carcinoma in the uterus and a multicentric thyroid papillary carcinoma in the thyroid gland were diagnosed.

  11. Positron emission tomography

    International Nuclear Information System (INIS)

    Wienhard, K.; Heiss, W.D.

    1984-01-01

    The principles and selected clinical applications of positron emission tomography are described. In this technique a chemical compound is labeled with a positron emitting isotope and its biochemical pathway is traced by coincidence detection of the two annihilation photons. The application of the techniques of computed tomography allows to reconstruct the spatial distribution of the radioactivity within a subject. The 18 F-deoxyglucose method for quantitative measurement of local glucose metabolism is discussed in order to illustrate the possibilities of positron emission tomography to record physiological processes in vivo. (orig.) [de

  12. beta-adrenergic effects on carbohydrate metabolism in the unweighted rat soleus muscle

    Science.gov (United States)

    Kirby, Christopher R.; Tischler, Marc E.

    1990-01-01

    The effect of unweighting on the response of the soleus-muscle carbohydrate metabolism to a beta-adrenergic agonist (isoproterenol) was investigated in rats that were subjected to three days of tail-cast suspension. It was found that isoproterenol promoted glycogen degradation in soleus from suspended rats to a higher degree than in weighted soleus from control rats, and had no effect in unweighted digitorum longus. However, isoproterenol did not have a greater inhibitory effect on the net uptake of tritium-labeled 2-deoxy-glucose by the unweighted soleus and that isoproterenol inhibited hexose phosphorylation less in the unweighted than in the control muscle.

  13. Progressive activation of paratrigeminal nucleus during entrance to hibernation

    International Nuclear Information System (INIS)

    Kilduff, T.S.; Sharp, F.R.; Heller, H.C.

    1988-01-01

    The paratrigeminal nucleus (Pa5) undergoes a progressive increase in its uptake of 2-[ 14 C]deoxyglucose (2DG) relative to other brain structures during entrance to hibernation in the ground squirrel. This highly significant increase results in the Pa5 becoming the most highly labeled brain region during hibernation, even though it exhibits one of the lowest levels of 2DG uptake in the brain during the nonhibernating state. The progressive activation of the Pa5 observed during entrance is reversed during arousal from hibernation. These observations and the neuroanatomical projections of the Pa5 implicate this nucleus as playing a role in the entrance and maintenance of the hibernating state

  14. FDG decomposition products

    International Nuclear Information System (INIS)

    Macasek, F.; Buriova, E.

    2004-01-01

    In this presentation authors present the results of analysis of decomposition products of [ 18 ]fluorodexyglucose. It is concluded that the coupling of liquid chromatography - mass spectrometry with electrospray ionisation is a suitable tool for quantitative analysis of FDG radiopharmaceutical, i.e. assay of basic components (FDG, glucose), impurities (Kryptofix) and decomposition products (gluconic and glucuronic acids etc.); 2-[ 18 F]fluoro-deoxyglucose (FDG) is sufficiently stable and resistant towards autoradiolysis; the content of radiochemical impurities (2-[ 18 F]fluoro-gluconic and 2-[ 18 F]fluoro-glucuronic acids in expired FDG did not exceed 1%

  15. Quantitative autoradiography of neurochemicals

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Biegon, A.; Bleisch, W.V.

    1982-01-01

    Several new methods have been developed that apply quantitative autoradiography to neurochemistry. These methods are derived from the 2-deoxyglucose (2DG) technique of Sokoloff (1), which uses quantitative autoradiography to measure the rate of glucose utilization in brain structures. The new methods allow the measurement of the rate of cerbral protein synthesis and the levels of particular neurotransmitter receptors by quantitative autoradiography. As with the 2DG method, the new techniques can measure molecular levels in micron-sized brain structures; and can be used in conjunction with computerized systems of image processing. It is possible that many neurochemical measurements could be made by computerized analysis of quantitative autoradiograms

  16. Reassessment of FDG uptake in tumor cells: High FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production

    Energy Technology Data Exchange (ETDEWEB)

    Waki, A.; Fujibayashi, Y.; Yonekura, Y.; Sadato, N.; Ishii, Y.; Yokoyama, A

    1997-10-01

    To determine appropriate use of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and {sup 3}H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

  17. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    -500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  18. Metastatic meningioma: positron emission tomography CT imaging findings.

    LENUS (Irish Health Repository)

    Brennan, C

    2010-12-01

    The imaging findings of a case of metastasing meningioma are described. The case illustrates a number of rare and interesting features. The patient presented with haemoptysis 22 years after the initial resection of an intracranial meningioma. CT demonstrated heterogeneous masses with avid peripheral enhancement without central enhancement. Blood supply to the larger lesion was partially from small feeding vessels from the inferior pulmonary vein. These findings correlate with a previously published case in which there was avid uptake of fluoro-18-deoxyglucose peripherally with lesser uptake centrally. The diagnosis of metastasing meningioma was confirmed on percutaneous lung tissue biopsy.

  19. Cerebral glucose metabolism in Parkinson's disease

    International Nuclear Information System (INIS)

    Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

    1984-01-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  20. Functional imaging of the brain with positron emission tomography

    International Nuclear Information System (INIS)

    Alavi, A.; Reivich, M.; Jones, S.C.; Greenberg, J.H.; Wolf, A.P.

    1982-01-01

    An extensive review, with 191 references, of the development and diagnostic use of positron emission tomography (PET) of the brain is presented. An historical overview of functional studies of the brain reviews the use of nitrons oxide, 85 Kr and 133 Xe, [ 14 C]2-deoxyglucose, and [ 18 F]FDG. The [ 18 F]FDG technique allows the investigation of the effects of physiologic stimulation on the brain. Several studies using this technique are reported. The effects of stroke, seizure disorders, aging and dementia, and schizophrenia on cerebral metabolism as demosntrated by PET are explored

  1. Transient epileptic amnesia differentiated from psychogenic "fugue": neuropsychological, EEG, and PET findings.

    Science.gov (United States)

    Kopelman, M D; Panayiotopoulos, C P; Lewis, P

    1994-08-01

    A patient had repeated episodes of transient loss of memory, which had been attributed to psychogenic causes. Preservation of his sense of personal identity and the presence of repetitive questioning indicated an organic basis, however, and the multiplicity of the attacks and their brief duration suggested an epileptic aetiology. Although three standard EEGs, CT and MRI were all normal, two sleep EEGs confirmed bilateral foci in the temporal lobes. The attacks responded to an anticonvulsant. A fluoro-deoxyglucose PET scan, performed a few months after the most recent attack, was normal. The patient also had impaired anterograde memory that persisted six months after recovery from the acute attacks.

  2. Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Jørgensen, Sebastian Beck; Rose, Adam John

    2009-01-01

    and female mice over-expressing kinase-dead alpha2-AMPK (AMPK-KD) in skeletal and heart muscles. Wildtype and AMPK-KD mice were exercised at the same absolute intensity and the same relative intensity (30% and 70% of individual maximal running speed) to correct for reduced exercise capacity of the AMPK......-KD mouse. Muscle glucose clearance was measured using [3H]-2-deoxy-glucose as tracer. In wildtype mice glucose clearance was increased at 30% and 70% of maximal running speed by 40% and 350% in the quadriceps muscle, and by 120% and 380% in gastrocnemius muscle, respectively. Glucose clearance...

  3. Electrocardiographic gating in positron emission computed tomography

    International Nuclear Information System (INIS)

    Hoffman, E.J.; Phelps, M.E.; Wisenberg, G.; Schelbert, H.R.; Kuhl, D.E.

    1979-01-01

    Electrocardiographic (ECG) synchronized multiple gated data acquisition was employed with positron emission computed tomography (ECT) to obtain images of myocardial blood pool and myocardium. The feasibility and requirements of multiple gated data acquisition in positron ECT were investigated for 13NH3, ( 18 F)-2-fluoro-2-D-deoxyglucose, and ( 11 C)-carboxyhemoglobin. Examples are shown in which image detail is enhanced and image interpretation is facilitated when ECG gating is employed in the data collection. Analysis of count rate data from a series of volunteers indicates that multiple, statistically adequate images can be obtained under a multiple gated data collection format without an increase in administered dose

  4. Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

    Science.gov (United States)

    Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

    2017-01-01

    A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Transformation of myelodysplastic syndrome to acute myeloid leukemia: a case with whole-body 2- (18F) fluoro-2-deoxy-D-glucose positron emission tomography

    International Nuclear Information System (INIS)

    Liu, Fang; Cao, Qinghua

    2011-01-01

    The case reported here was that of an old woman characterized by pancytopenia, chromosome clonal abnormality, fluctuation of the percent of blast cells at 20%, and negative evidence of malignancy in whole-body 2-( 18 F) fluoro-2-deoxy-D-glucose positron emission tomography ( 18 F-FDG PET). After about 10 months, the blast cells accounted for about 25%, the morphology of which was similar to that of previous ones, and 18 F-FDG PET demonstrated diffusing increased uptake in the right upper leg and lymph nodes and patchy high uptake of bone marrow. 2-( 18 F)-fluoro-2-deoxyglucose can reflect extramedullary infiltration and bone marrow cellularity of the whole body, compared with invasive, regional biopsies and aspirations. The value of 2-( 18 F)-fluoro-2-deoxyglucose or 3'-deoxy-3'-( 18 F)-fluorothymidine positron emission tomography as an indicator in predicting the transformation of myelodysplastic syndrome to acute myeloid leukemia needs to be explored in the future. (author)

  6. Neuroimaging Findings in a Brain With Niemann–Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Jei-Yie Huang

    2011-08-01

    Full Text Available Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI, magnetic resonance spectrography (MRS and 18-fluoro-2-deoxyglucose positron emission tomography (PET imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

  7. Catecholamine stimulation, substrate competition, and myocardial glucose uptake in conscious dogs assessed with positron emission tomography

    International Nuclear Information System (INIS)

    Merhige, M.E.; Ekas, R.; Mossberg, K.; Taegtmeyer, H.; Gould, K.L.

    1987-01-01

    Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2- 18 F]-2-deoxyglucose (FDG) and 82 Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82 Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition

  8. Co-induction of glucose regulated proteins and adriamycin resistance in Chinese hamster cells

    International Nuclear Information System (INIS)

    Shen, J.; Hughes, C.; Cai, J.; Bartels, C.; Gessner, T.; Subjeck, J.

    1987-01-01

    Glucose deprivation, anoxia, calcium ionophore A23187 or 2-deoxyglucose all inducers of glucose regulated proteins (grps), also lead to a significant induction of resistance to the drug adriamycin. In the case of anoxia, A23187 and 2-deoxyglucose, the induction of resistance correlates with both the application of the inducing stress and the induction of grps. In the case of glucose deprivation, the onset of resistance correlates with the onset of glucose deprivation and precedes grp induction. Removal of each grp including condition results in the rapid disappearance of this resistance in a manner which correlates with the repression of the grps. This drug resistance can be induced in confluent cells or in actively proliferating cells, although the effect is greater in the more sensitive proliferating cells. Induction of heat shock proteins (hsps) does not appear to lead to any major change in adriamycin resistance. Grp induced cells retain less adriamycin than do controls with the greatest reduction occurring during anoxia, which is also the strongest inducer of grps and resistance. The authors propose that the application of a grp inducing stress leads to a concurrent induction in drug resistance, possibly via the translocation of grps in the cell. Finally, they also observed that adriamycin itself can induce both hsps and grps. It is possible that adriamycin exposure may correspondingly induce auto-resistance

  9. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

    Science.gov (United States)

    Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

    2016-10-01

    Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

  10. Glucose utilisation in the lungs of septic rats

    International Nuclear Information System (INIS)

    Hansson, L.; Jeppsson, B.; Ohlsson, T.; Sandell, A.; Valind, S.; Luts, A.; Wollmer, P.

    1999-01-01

    Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ( 18 FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of 18 FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. 18 FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions. (orig.)

  11. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.

    2016-05-03

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

  12. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

    Directory of Open Access Journals (Sweden)

    Scorza Fulvio Alexandre

    2002-01-01

    Full Text Available Status epilepticus (SE is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%, caudate-putamen (+30.6%, frontoparietal cortex (+32.2%, amygdala (+31.7%, entorrinal cortex (+28.2%, thalamic nucleus (+93.5%, pre-tectal area (+50.1% and substantia nigra (+50.3% when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  13. Preventing Allograft Rejection by Targeting Immune Metabolism

    Directory of Open Access Journals (Sweden)

    Chen-Fang Lee

    2015-10-01

    Full Text Available Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG, the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON. Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models.

  14. Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess.

    Science.gov (United States)

    Sato, Jun; Kuroshima, Takeshi; Wada, Mayumi; Satoh, Akira; Watanabe, Shiro; Okamoto, Shozo; Shiga, Tohru; Tamaki, Nagara; Kitagawa, Yoshimasa

    2016-05-01

    This study describes the use of (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA.

  15. A novel description of FDG excretion in the renal system: application to metformin-treated models

    Science.gov (United States)

    Garbarino, S.; Caviglia, G.; Sambuceti, G.; Benvenuto, F.; Piana, M.

    2014-05-01

    This paper introduces a novel compartmental model describing the excretion of 18F-fluoro-deoxyglucose (FDG) in the renal system and a numerical method based on the maximum likelihood for its reduction. This approach accounts for variations in FDG concentration due to water re-absorption in renal tubules and the increase of the bladder’s volume during the FDG excretion process. From the computational viewpoint, the reconstruction of the tracer kinetic parameters is obtained by solving the maximum likelihood problem iteratively, using a non-stationary, steepest descent approach that explicitly accounts for the Poisson nature of nuclear medicine data. The reliability of the method is validated against two sets of synthetic data realized according to realistic conditions. Finally we applied this model to describe FDG excretion in the case of animal models treated with metformin. In particular we show that our approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin.

  16. {sup 18}FDG PET and acetazolamide-enhanced {sup 99m}Tc-HMPAO SPET in systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Gruenwald, F. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Schomburg, A. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Badali, A. [Dept. of Dermatology, Univ. of Bonn (Germany); Ruhlmann, J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Pavics, L. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Biersack, H.J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin

    1995-09-01

    In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) and a PET scan with fluorine-18 deoxyglucose ({sup 18}FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that ``preclinical`` CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE. (orig.). With 2 figs.

  17. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  18. Quantitative densitometry of neurotransmitter receptors

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

    1982-01-01

    An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

  19. Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

    Science.gov (United States)

    Chao, Julie; Weathersbee, Carolyn J.

    1974-01-01

    Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

  20. [Fluorodeoxiglucose F18 positron emission tomography imaging (F18FDG) for the assessment of rising levels of serum CA 19-9 in pancreatic mucinous cystadenocarcinoma. Report of one case].

    Science.gov (United States)

    Canessa, José A; Larach, Jorge A; Massardo, Teresa; Parra, Juan; Jofré, Josefina; González, Patricio; Morales, Bernardo; Humeres, Pamela; Sierralta, Paulina; Galaz, Rodrigo

    2004-03-01

    We report a 38 year old female patient with a pancreatic mucinous cystadenocarcinoma. She presented at the onset with a peritoneal rupture that required emergency surgery. Five months later, the patient was subjected to a segmental pancreatectomy and splenectomy. One year later, the patient had a serious gastric bleeding secondary to a gastric ulcer. Due to a persistent increase in her CA 19-9 levels, a Positron Emission Tomography (PET) functional imaging with fluorine 18-deoxyglucose (F18FDG) was done. It showed an intense focal hypermetabolism in the gastric wall reported as a secondary tumour location. The patient was subjected to a total gastrectomy and Roux en Y anastomosis, with a good outcome. The pathological study confirmed the presence of a metastasis of an adenocarcinoma in the gastric wall. The relative value of CA 19-9 markers and FDG PET in pancreatic and gastric carcinomas is discussed.

  1. Pin Diode Detector For Radiation Field Monitoring In A Current Mode

    International Nuclear Information System (INIS)

    Beck, A.; Wengrowicz, U.; Kadmon, Y.; Tirosh, D.; Osovizky, A.; Vulasky, E.; Tal, N.

    1999-01-01

    Thus paper presents calculations and tests made for a detector based on a bare Pin diode and a Pin diode coupled to a plastic scintillator. These configurations have a variety of applications in radiation field monitoring. For example, the Positron Emission Tomography (PET) technology which becomes an established diagnostic imaging modality. Flour-18 is one of the major isotopes being used by PET imaging. The PET method utilizes short half life β + radioisotopes which, by annihilation, produce a pair of high energy photons (511 keV). Fluoro-deoxyglucose producers are required to meet federal regulations and licensing requirements. Some of the regulations are related to the production in chemistry modules regarding measuring the Start Of Synthesis (SOS) activity and verifying the process repeatability. Locating a radiation detector based on Pin diode inside the chemistry modules is suitable for this purpose. The dimensions of a Pin diode based detector can be small, with expected linearity over several scale decades

  2. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    International Nuclear Information System (INIS)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr.; Gillin, J.C.

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep

  3. Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

    Science.gov (United States)

    Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

    1995-02-06

    EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

  4. Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

    Science.gov (United States)

    Bock, J; Breuer, S; Poeggel, G; Braun, K

    2017-03-01

    In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

  5. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

    International Nuclear Information System (INIS)

    Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

    1985-01-01

    Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities

  6. Metabolic rate in different rat brain areas during seizures induced by a specific delta opiate receptor agonist.

    Science.gov (United States)

    Haffmans, J; De Kloet, R; Dzoljic, M R

    1984-06-04

    The glucose utilization during specific delta opiate agonist-induced epileptiform phenomena, determined by the [14C]2-deoxyglucose technique (2-DG), was examined in various rat brain areas at different time intervals. The peak in EEG spiking response and the most intensive 2-DG uptake occurred 5 min after intraventricular (i.v.t.) administration of the delta opiate receptor agonist. The most pronounced 2-DG uptake at this time interval can be observed in the subiculum, including the CA1 hippocampal area, frontal cortex and central amygdala. A general decrease of glucose consumption, compared to control values, is observed after 10 min, in all regions, with exception of the subiculum. Since functional activity and 2-DG uptake are correlated, we suggest that the subiculum and/or CA1 area, are probably the brain regions most involved in the enkephalin-induced epileptic phenomena.

  7. [11C] labeled erlotinib as a new radiotracer for identification of patients responding to erlotinib treatment

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; Weber, Britta; Jakobsen, Steen

    2009-01-01

    Erlotinib (Tarceva®) is a tailored drug targeting the Epidermal Growth Factor Receptor (EGFR), which is commonly overexpressed in various human cancers including lung cancer. The purpose of this study was to develop a method for identification of lung cancer patients that respond to erlotinib...... the accumulation of [11C] erlotinib was higher in the tumor than in all other organs except the liverwhich is the main organ of erlotinib metabolism (Cancer Research, 2009 69: 873-878). We have now extended this study to patients with the aim to identify the subset of patients that will respond to Erlotinib...... treatment (10-15 %). Tumors were identified by routine CT scan and [18F]-2-fluoro- 2-deoxyglucose (FDG) PET/CT and compared with [11C] erlotinib PET/CT. As expected, all patients examined so far (n=4) showed [18F] FDG uptake. Our results with [11C] erlotinib show that tumors can be identified by [11C...

  8. A Pictorial Review on Extraosseous Manifestations of Multiple Myelomas

    International Nuclear Information System (INIS)

    Seo, Jung Min; Lee, Kyung Soo; Yi, Chin A; Kim, Seong Hyun; Park, Byung Kwan; Han, Boo Kyung; Kim, Hyung Jin

    2011-01-01

    Extraosseous involvement of multiple myelomas can be seen clinically or radiologically in approximately 10-20% of patients at the time of initial diagnosis and may develop in an additional 15% of patients over the course of the disease. The condition can arise in any tissue of the body and its presence has been associated with more aggressive disease, a guarded prognosis, or high-dose chemotherapy. Imaging findings of extraosseous multiple myelomas are diverse. They usually show high enhancement on contrast-medium enhanced CT scans, exhibit iso-signal intensity on both T1- and T2- weighted images, and variable 18F-fluorine deoxyglucose (FDG) uptake at PET. The disease may simulate an infectious condition since it may be concurrent with underlying multiple myelomas per se or it may occur during myeloma treatment including stem cell transplantation.

  9. FDG-PET in Follicular Lymphoma Management

    Directory of Open Access Journals (Sweden)

    C. Bodet-Milin

    2012-01-01

    Full Text Available 18-Fluoro-deoxyglucose positron emission tomography/computerised tomography (FDG PET/CT is commonly used in the management of patients with lymphomas and is recommended for both initial staging and response assessment after treatment in patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Despite the FDG avidity of follicular lymphoma (FL, FDG PET/CT is not yet applied in standard clinical practice for patients with FL. However, FDG PET/CT is more accurate than conventional imaging for initial staging, often prompting significant management change, and allows noninvasive characterization to guide assessment of high-grade transformation. For restaging, FDG PET/CT assists in distinguishing between scar tissue and viable tumors in residual masses and a positive PET after induction treatment would seem to predict a shorter progression-free survival.

  10. Cerebroprotective activity of U-50488H: Relationship to interactions with excitatory amino acids and calcium

    International Nuclear Information System (INIS)

    Camacho Ochoa, M.

    1987-01-01

    The mechanism underlying the anticonvulsant and cerebroprotective activity of U-50488H was evaluated using 45 Ca ++ uptake in rat Ficoll purified synaptosomes, ( 3 H)-2-deoxyglucose uptake in selected mouse brain regions, ( 3 H)kainic acid binding to mouse forebrain synaptic membranes and incidence of KA-induced lesions in the CA3 region of the mouse hippocampus. U-50488H causes reduction in K + -evoked 45 Ca ++ uptake. These effects are comparable to those of the calcium channel blockers verapamil and nifedipine and seem to be related to calcium dependent mechanisms. Changes in saturability, specificity and dissociation constant values of kainic acid receptor binding were demonstrated in the presence of U-50488H at concentrations similar to those used in 45 Ca ++ uptake studies and in the presence of calcium and chloride ions

  11. Role of -FDG PET Scan in Rheumatoid Lung Nodule: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Christine L. Chhakchhuak

    2013-01-01

    Full Text Available Flourine-18 fluoro-2-deoxy-glucose (18F-FDG positron emission tomography combined with computed tomography (PET/CT is a useful test for the management of malignant conditions. Inflammatory and infectious processes, however, can cause increased uptake on PET scanning, often causing diagnostic dilemmas. This knowledge is important to the rheumatologist not only because of the inflammatory conditions we treat but also because certain rheumatic diseases impose an increased risk of malignancy either due to the disease itself or as a consequence of medications used to treat the rheumatic diseases. There is an increasing body of evidence investigating the role of PET scans in inflammatory conditions. This paper describes a patient with rheumatoid arthritis who developed pulmonary nodules that showed increased uptake on PET/CT scan and reviews the use of PET scanning in the diagnosis and management of rheumatoid arthritis.

  12. Change in the diagnosis from classical Hodgkin's lymphoma to anaplastic large cell lymphoma by 18F flourodeoxyglucose positron emission tomography/computed tomography: Importance of recognising disease pattern on imaging and immunohistochemistry

    International Nuclear Information System (INIS)

    Senthil, Raja; Mohapatra, Ranjan Kumar; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare type of nonHodgkin's lymphoma (NHL), but one of the most common subtypes of T-cell lymphoma. It is an aggressive T-cell lymphoma, and some ALCL may mimic less aggressive classical HL histopathlogically. It may be misdiagnosed unless careful immunohistochemical examination is performed. As the prognosis and management of these two lymphomas vary significantly, it is important to make a correct diagnosis. We describe a case who was diagnosed as classical HL by histopathological examination of cervical lymph node, in whom 18 F-flouro deoxyglucose positron emission tomography/computed tomography appearances were unusual for HL and warranted review of histopathology that revealed anaplastic lymphoma kinase-1 negative anaplastic large T-cell lymphoma, Hodgkin-like variant, thereby changing the management

  13. Emission computed tomography: methodology and applications

    International Nuclear Information System (INIS)

    Reivich, M.; Alavi, A.; Greenberg, J.; Fowler, J.; Christman, D.; Rosenquist, A.; Rintelmann, W.; Hand, P.; MacGregor, R.; Wolf, A.

    1980-01-01

    A technique for the determination of local cerebral glucose metabolism using positron emission computed tomography is described as an example of the development of use of this methodology for the study of these parameters in man. The method for the determination of local cerebral glucose metabolism utilizes 18 F-2-fluoro-2-deoxyglucose ([ 18 F]-FDG). In this method [ 18 F]-FDG is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissue. The labelled product of metabolism, [ 18 F]-FDG phosphate, is essentially trapped in the tissue over the time course of the measurement. The studies demonstrate the potential usefulness of emission computed tomography for the measurement of various biochemical and physiological parameters in man. (Auth.)

  14. PET/CT for atherosclerotic plaque imaging

    International Nuclear Information System (INIS)

    Ben-Haim, S.; Technion Institute of Technology, Haifa; Israel, O.; Rambam Medical Center, Haifa

    2006-01-01

    Atherosclerosis is one of the leading causes of morbidity and mortality in the world. Rupture of atherosclerotic plaques and thrombi formation are the primary mechanisms of myocardial infarction or cerebrovascular accident. Angiography is considered to represent the gold standard technique for imaging of the arterial lumen. However, in recent years it has been realized that the primary determinant of the atherosclerotic plaque stability is the composition of the plaque and other imaging modalities have been suggested. The purpose of this review is to briefly summarize the knowledge accumulated to present date regarding the potential role of fluo deoxyglucose imaging in the assessment of atherosclerosis and to compare this modality to additional available imaging approaches for the detection of vulnerable plaques

  15. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  16. Ethanol production kinetics by a thermo-tolerant mutant of saccharomyces cerevisiae from starch industry waste (hydrol)

    International Nuclear Information System (INIS)

    Shah, F.A.; Aziz, S.

    2010-01-01

    A thermo-tolerant and deoxyglucose-resistant mutant of Saccharomyces cerevisiae was developed and employed to convert them to fuel ethanol in a 150 litre fermenter. Maximum ethanol production was achieved when fermentation of dextrozyme- treated hydrol was carried out for about 36 hours under optimized fermenting conditions. The maximum specific ethanol production rate (qP), and overall ethanol yield (YP/S) were found to be 2.82 g L/sup -1/ h/sup -1/ and 0.49 g/g respectively. Determination of activation energy for cell growth (Ea= 20.8 kJ/mol) and death (Ed = 19.1 kJ/mol) and product formation and inactivation (EP=35.8 kJ/mol and Edp = 33.5 kJ/mol) revealed the thermo-stability of the organism for up to 47 deg. C. (author)

  17. Benign thyroid and neck lesions mimicking malignancy with false positive findings on positron emission tomography-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ye Ri; Kim, Shin Young; Lee, Sang Mi [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of); Lee, Deuk Young [Dept. of Surgery, Younsei Angelot Women' s Clinic, Cheonan (Korea, Republic of)

    2017-02-15

    The increasing use of positron emission tomography-computed tomography (PET/CT) has led to the frequent detection of incidental thyroid and neck lesions with increased 18F-deoxyglucose (FDG) uptake. Although lesions with increased FDG uptake are commonly assumed to be malignant, benign lesions may also exhibit increased uptake. The purpose of this pictorial essay is to demonstrate that benign thyroid and neck lesions can produce false-positive findings on PET/CT, and to identify various difficulties in interpretation. It is crucial to be aware that differentiating between benign and malignant lesions is difficult in a considerable proportion of cases, when relying only on PET/CT findings. Correlation of PET/CT findings with additional imaging modalities is essential to avoid misdiagnosis.

  18. Usefulness of positron emission tomography (TEP) in the assessment of osteo-articular prosthesis; Utilite de la tomographie par emission de positons (TEP) dans l'etude des protheses osteo-articulaires

    Energy Technology Data Exchange (ETDEWEB)

    Maldonado, A.; Suarez, J.P.; Dominguez, M.L. [Centro PET Complutense, Madrid (Spain)

    2004-12-15

    Joint arthroplasty is performed with increasing frequency as the population ages. Loosening or infection of the prosthesis is a relatively common event that can limit the lifetime of a prosthesis. Accuracy differentiation between aseptic and septic loosening of the prosthesis remains a challenge because of the consequences for patient management. Moreover, an early diagnosis of infected hip prosthesis is very important for optimal and cost-effective management. Various approaches have developed to visualize infection and inflammation by nuclear medicine techniques. Recently positron emission tomography (PET) with fluorine-l8 labelled 2 fluoro-2-deoxyglucose ({sup 18}F-FDG) has been shown to delineate infectious and inflammatory foci with high sensitivity owing to the increased glucose metabolism in inflammatory cells. In this paper we review the role of FDG-PET in this common differential diagnosis in patients with total knee and hip prostheses. Different patterns of FDG-PET interpretation have been described as wed as methodological aspects. (author)

  19. Cerebral glucose metabolic differences in patients with panic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M. (NIMH, Bethesda, MD (USA))

    1990-08-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.

  20. Cerebral glucose metabolic differences in patients with panic disorder

    International Nuclear Information System (INIS)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M.

    1990-01-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task

  1. Perturbations of NAD+ salvage systems impact mitochondrial function and energy homeostasis in mouse myoblasts and intact skeletal muscle

    DEFF Research Database (Denmark)

    Andersen, Marianne Agerholm; Dall, Morten; Jensen, Benjamin Anderschou Holbech

    2018-01-01

    Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (sh......Nampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity...... was reduced by 25%. Moreover, anaerobic glycolytic flux increased by 55% and 2-deoxyglucose uptake increased by 25% in shNampt KD cells. Treatment with the NAD+ precursor nicotinamide riboside restored NAD+ levels in shNampt cells and increased maximal respiratory capacity by 18% and 32% in control and sh...

  2. Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85alpha

    DEFF Research Database (Denmark)

    Almind, Katrine; Delahaye, Laurent; Hansen, Torben

    2002-01-01

    . When the four human p85alpha proteins were expressed in yeast, a 27% decrease occurred in the level of protein expression of p85alpha(Ile/Asp) (P = 0.03) and a 43% decrease in p85alpha(Ile/Asn) (P = 0.08) as compared with p85alpha(Met/Asp). Both p85alpha(Ile/Asp) and p85alpha(Ile/Asn) also exhibited...... increased binding to phospho-insulin receptor substrate-1 by 41% and 83%, respectively (P substrate-1 slightly increased in brown preadipocytes derived from p85alpha...... knockout mice. Both p85alpha(Met) and p85alpha(Ile) had similar effects on AKT activity and were able to reconstitute differentiation of the preadipocytes, although the triglyceride concentration in fully differentiated adipocytes and insulin-stimulated 2-deoxyglucose uptake were slightly lower than...

  3. Positron emission tomography for the assessment of myocardial viability

    International Nuclear Information System (INIS)

    Schelbert, H.R.

    1991-01-01

    The detection of viable myocardium or ischemically injured myocardium with a reversible impairment of contractile function remains clinically important but challenging. Detection of reversible dysfunction and distinction from irreversible tissue injury by positron emission tomography is based on identification of preserved or even enhanced glucose metabolism with F-18 2-fluoro 2-deoxyglucose. Regional patterns of myocardial glucose utilization and blood flow, defined as perfusion-metabolism mismatches or matches, on positron emission tomography in patients with chronic or even acute ischemic heart disease are highly accurate in predicting the functional outcome after interventional revascularization. Compared with thallium-201 redistribution scintigraphy, positron emission tomography appears to be diagnostically more accurate, especially in patients with severely impaired left ventricular function. While larger clinical trials are needed for further confirmation, positron emission tomography has already proved clinically useful for stratifying patients with poor left ventricular function to the most appropriate therapeutic approach

  4. Nuclear medicine and imaging research: quantitative studies in radiopharmaceutical science. Comprehensive progress report, January 1, 1980-December 31, 1982

    International Nuclear Information System (INIS)

    Beck, R.N.; Cooper, M.C.

    1982-06-01

    This 3-y report cites progress in the following areas of radiopharmaceutical research: cyclotron operations; 51 Mn for myocardial localization; 82 Rb for heart imaging; 15 O-labelled H 2 O and molecular oxygen; studies on 11 C-2-deoxyglucose localization; 13 NH 3 measurements of myocardial perfusion; 130 Cs myocardial imaging; heart motion studies; labelled amino acids for pancreatic imaging; 11 C-hexamethonium for cartilage imaging; 11 C-cholic acid pharmacology; blood element labelling with /sup 115m/In; 75 Br studies; extrapolation of animal data to humans; in vivo quantification of radioactivity; fetal and neonatal radiation effects from radiopharmaceuticals administered to pregnant and lactating mice; and verification of MIRD absorbed dose calculations for some organ-incorporated radionuclides

  5. Patterns of brain activity in normals and schizophrenics with positron emission tomography

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wolf, A.P.; Gomez-Mont, F.; Brodie, J.D.; Canero, R.; Van Gelder, P.; Russell, J.A.G.

    1985-01-01

    The authors investigated the functional interaction among brain areas under baseline and upon activation by a visual task to compare the response of normal subjects from the ones of chronic schizophrenics. Cerebral metabolic images were obtained on twelve healthy volunteers an eighteen schizophrenics with positron emission tomography and 11-C-Deoxyglucose. Correlation coefficients among the relative metabolic values (region of interest divided by the average of whole brain gray matter) of 11 brain regions; frontal, parietal, temporal and occipital left and right lobes, left and right basal ganglia and thalamus were computed for the baseline and for the task. Under baseline, normals showed more functional correlations than schizophrenics. Both groups showed a thalamo-occipital (positive) and thalamo-frontal (negative) interaction. The highest correlations among homologous brain areas were the frontal, occipital and basal ganglia

  6. Smoking normalizes cerebral blood flow and oxygen consumption after 12-hour abstention

    DEFF Research Database (Denmark)

    Seyedi Vafaee, Manouchehr; Gjedde, Albert; Imamirad, Nasrin

    2015-01-01

    Acute nicotine administration stimulates [14C]deoxyglucose trapping in thalamus and other regions of rat brain, but acute effects of nicotine and smoking on energy metabolism have rarely been investigated in human brain by positron emission tomography (PET). We obtained quantitative PET...... of the abstention period, global grey-matter CBF and CMRO2 were both reduced by 17% relative to nonsmokers. At 15 minutes after renewed smoking, global CBF had increased insignificantly, while global CMRO2 had increased by 11%. Regional analysis showed that CMRO2 had increased in the left putamen and thalamus......, and in right posterior cortical regions at this time. At 60 and 105 minutes after smoking resumption, CBF had increased by 8% and CMRO2 had increased by 11–12%. Thus, we find substantial and global impairment of CBF/CMRO2 in abstaining smokers, and acute restoration by resumption of smoking. The reduced CBF...

  7. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-04-23

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

  8. Ethanol Production Kinetics by a Thermo-Tolerant Mutant of Saccharomyces Cerevisiae from Starch Industry Waste (Hydrol

    Directory of Open Access Journals (Sweden)

    Farman Ali Shah

    2010-06-01

    Full Text Available A thermo-tolerant and deoxyglucose-resistant mutant of Saccharomyces cerevisiae was developed and employed to convert them to fuel ethanol in a 150 litre fermenter. Maximum ethanol production was achieved when fermentation of dextrozyme- treated hydrol was carried out for about 36 hours under optimized fermenting conditions. The maximum specific ethanol production rate (qP, and overall ethanol yield (YP/S were found to be 2.82 g L-1 h-1 and 0.49 g/g respectively. Determination of activation energy for cell growth (Ea= 20.8 kJ/mol and death (Ed = 19.1 kJ/mol and product formation and inactivation (EP=35.8 kJ/mol and Edp = 33.5 kJ/mol revealed the thermo-stability of the organism for up to 47°C.

  9. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    and neurological disability. METHODS: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically......OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...... deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction...

  10. Positron emission tomography in pre-surgical evaluation of partial epilepsy in adults

    International Nuclear Information System (INIS)

    Semah, F.; Dupont, S.

    1999-01-01

    Positron emission tomography (PET) may be used to map regional cerebral glucose metabolism using 18 F-deoxyglucose in patients with partial epilepsy. An area of reduced glucose metabolism, that is commonly more extensive than the underlying anatomical abnormality, is found in most of the patients with medically refractory partial epilepsy. These functional lesions are very useful in the delineation of the epileptogenic focus prior to surgery. PET may also be used to demonstrate abnormalities in the binding of specific ligands, such as 11 C-flumazenil, to the central benzodiazepine-GABA A receptor complex. Focal decreases in benzodiazepine receptor binding is commonly seen at an epileptic focus, in a more restricted distribution than the area of hypo-metabolism. (author)

  11. Bone and bone marrow - nuclear medicine in the diagnosis of disorders of the hematopoetic system

    International Nuclear Information System (INIS)

    Cremerius, U.

    1997-01-01

    Significant progress has been achieved during the last years regarding therapy of neoplastic and non-neoplastic diseases of the hematopoietic system by introduction of new therapeutic modalities like highdose chemotherapy, bone marrow and stem cell transplantation, interferon-therapy and others. Diagnosis is still based on biopsy and histopathology of bone marrow. Imaging methods, however, provided by radiology and nuclear medicine, are now increasingly employed to give an additional macroscopic view over morphological and functional changes of the entire bone marrow. Bone marrow scintigraphy either using radiocolloids or immunoscintigraphy against granulocyte-antigenes may be performed as an alternative or an addition to nuclear magnetic resonance imaging. Bone scintigraphy has been successful in the detection of additional bony lesions for more than two decades. Positron emission tomography using 18-fluorine-deoxyglucose has recently been employed as a new and promising tool also for assessment of bone marrow infiltration in malignant lymphomas. (orig.) [de

  12. A novel description of FDG excretion in the renal system: application to metformin-treated models

    International Nuclear Information System (INIS)

    Garbarino, S; Caviglia, G; Piana, M; Sambuceti, G; Benvenuto, F

    2014-01-01

    This paper introduces a novel compartmental model describing the excretion of 18F-fluoro-deoxyglucose (FDG) in the renal system and a numerical method based on the maximum likelihood for its reduction. This approach accounts for variations in FDG concentration due to water re-absorption in renal tubules and the increase of the bladder’s volume during the FDG excretion process. From the computational viewpoint, the reconstruction of the tracer kinetic parameters is obtained by solving the maximum likelihood problem iteratively, using a non-stationary, steepest descent approach that explicitly accounts for the Poisson nature of nuclear medicine data. The reliability of the method is validated against two sets of synthetic data realized according to realistic conditions. Finally we applied this model to describe FDG excretion in the case of animal models treated with metformin. In particular we show that our approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin. (paper)

  13. Extensive Tattoos Mimicking Lymphatic Metastasis on Positron Emission Tomography Scan in a Patient With Cervical Cancer.

    Science.gov (United States)

    Grove, Narine; Zheng, Ma; Bristow, Robert E; Eskander, Ramez N

    2015-07-01

    Positron emission tomography (PET) fused with computed tomography (CT) imaging is common in the clinical assessment of patients with locally advanced cervical cancer. Limitations to the utilization and interpretation of PET-CT scans in patients with cervical cancer have been described, including false-positive findings secondary to tattoo ink. A 32-year-old woman presented with clinical stage 1B1 cervical cancer and extensive tattoos of the lower extremities. Preoperative PET-CT scan identified two ileac lymph nodes with increased fluorine-18-deoxyglucose uptake suspicious for metastatic disease. At the time of surgical resection, bilateral pigmented lymph nodes were identified with histologic examination showing deposition of tattoo ink and no malignant cells. Physicians should be cognizant of the possible effects of tattoos on PET-CT findings while counseling patients and formulating a treatment program.

  14. Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

    Science.gov (United States)

    Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

    2000-09-01

    A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

  15. Usefulness of positron emission tomography (TEP) in the assessment of osteo-articular prosthesis

    International Nuclear Information System (INIS)

    Maldonado, A.; Suarez, J.P.; Dominguez, M.L.

    2004-01-01

    Joint arthroplasty is performed with increasing frequency as the population ages. Loosening or infection of the prosthesis is a relatively common event that can limit the lifetime of a prosthesis. Accuracy differentiation between aseptic and septic loosening of the prosthesis remains a challenge because of the consequences for patient management. Moreover, an early diagnosis of infected hip prosthesis is very important for optimal and cost-effective management. Various approaches have developed to visualize infection and inflammation by nuclear medicine techniques. Recently positron emission tomography (PET) with fluorine-l8 labelled 2 fluoro-2-deoxyglucose ( 18 F-FDG) has been shown to delineate infectious and inflammatory foci with high sensitivity owing to the increased glucose metabolism in inflammatory cells. In this paper we review the role of FDG-PET in this common differential diagnosis in patients with total knee and hip prostheses. Different patterns of FDG-PET interpretation have been described as wed as methodological aspects. (author)

  16. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Stöckli, Jacqueline; Meoli, Christopher C; Hoffman, Nolan J

    2015-01-01

    Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated...... weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise endurance...... together with impaired exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers....

  17. Use of PET/CT instead of CT-only when planning for radiation therapy does not notably increase life years lost in children being treated for cancer

    DEFF Research Database (Denmark)

    Kornerup, Josefine S.; Brodin, Nils Patrik; Christensen, Charlotte Birk

    2015-01-01

    BACKGROUND: PET/CT may be more helpful than CT alone for radiation therapy planning, but the added risk due to higher doses of ionizing radiation is unknown. OBJECTIVE: To estimate the risk of cancer induction and mortality attributable to the [F-18]2-fluoro-2-deoxyglucose (FDG) PET and CT scans...... used for radiation therapy planning in children with cancer, and compare to the risks attributable to the cancer treatment. MATERIALS AND METHODS: Organ doses and effective doses were estimated for 40 children (2-18 years old) who had been scanned using PET/CT as part of radiation therapy planning....... Multivariate linear regression was performed to find predictors for a high contribution to life years lost from the radiation therapy planning diagnostics. RESULTS: The mean contribution from PET to the effective dose from one PET/CT scan was 24% (range: 7-64%). The average proportion of life years lost...

  18. Clinical applications of positron emission tomography at Montreal Neurological Institute

    International Nuclear Information System (INIS)

    Morgan, P.P.

    1983-01-01

    The Montreal Neurological Institute occupies a leading position in positron emission tomography (PET) of the brain with the help of the following three techological gains: they have acquired a 'Therascan' positron emission tomograph manufactured by Atomic Energy of Canada Ltd.; also, a 'Baby Cyclotron' manufactured by Japan Steel Works Ltd.; and they have written a computer program to display the results in colour. Four short-lived isotopes are used; 11 C, 15 O, 18 F, 13 N. Studies of the oxygen uptake of tumours, their glucose metabolism (as monitored by 18 F labelled 2-fluoro-2-deoxyglucose), and their uptake of therapeutic agents, provide valuable research and diagnostic information. PET is also being used to study epilepsy and cerebrovascular disease

  19. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Science.gov (United States)

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  20. A strategy for obtaining both resting and psychologically activated state metabolic data from a single PET study using [F-18]-fluorodeoxyglucose(FDG)

    International Nuclear Information System (INIS)

    Chang, J.; Duara, R.; Barker, W.; Apicella, A.; Gilson, A.

    1985-01-01

    When psychological activation is studied with PET using the deoxyglucose method, a stable and specific psychological state for at least 30 minutes is required before commencing the scan. At this time, if the subject reverts to the testing state, a progressive degradation of the activated pattern occurs. However, a strategy could be used to obtain corrected activation state data and resting state data in a single study using a tracer such as FDG. The amount of tracer FDG and FDG-6P in the tissue at the time of study completion, t, will be the sum of the remaining quantity (R) of tracer accumulated in the tissue at the time T, when activation ceases, and the uptake during the subsequent period t-T when resting state glucose transport kinetics apply

  1. Clinical cardiac positron emission tomography: State of the art

    International Nuclear Information System (INIS)

    Gould, K.L.

    1991-01-01

    Cardiac positron emission tomography (PET) has evolved rapidly from a relatively esoteric research tool into clinical applications providing unique, quantitative information on myocardial perfusion, metabolism, and cell membrane function and having a potentially significant impact on cardiovascular medicine. Although there are many different positron radionuclides for imaging diverse myocardial behavior, three radionuclides have reached accepted clinical utility. Cardiac PET using nitrogen-13-ammonia, rubidium-82, and fluoro-18-deoxyglucose has proved accurate and definitive in multiple university and private-practice sites for diagnosing and assessing severity and location of coronary artery disease in symptomatic or asymptomatic patients, for identifying injured but viable myocardium potentially salvageable by revascularization, and for ruling out clinically significant coronary artery stenosis with a high specificity in patients who might otherwise undergo coronary arteriography to document the absence of significant disease. 89 references

  2. Basic principles and applications of {sup 18}F-FDG-PET/CT in oral and maxillofacial imaging: A pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Omami, Galal [Dept. of Oral Diagnosis and Polyclinics, Faculty of Dentistry, The Hong Kong University, Hong Kong (Hong Kong); Tamimi, Dania [BeamReaders Inc., Orlando (United States); Branstette, Barton F. [Dept. of Otolaryngology and Radiology, University of Pittsburgh School of Medicine, Pittsburgh (United States)

    2014-12-15

    A combination of positron emission tomography (PET) with 18F-labeled fluoro-2-deoxyglucose ({sup 18}F-FDG) and computed tomography ({sup 18}F-FDG-PET/CT) has increasingly become a widely used imaging modality for the diagnosis and management of head and neck cancer. On the basis of both recent literature and our professional experience, we present a set of principles with pictorial illustrations and clinical applications of FDG-PET/CT in the evaluation and management planning of squamous cell carcinoma of the oral cavity and oropharynx. We feel that this paper will be of interest and will aid the learning of oral and maxillofacial radiology trainees and practitioners.

  3. Control of the cerebral circulation and metabolism by the rostral ventrolateral medulla: Possible role in the cerebrovascular response to hypoxia

    International Nuclear Information System (INIS)

    Underwood, M.D.

    1988-01-01

    Neurons within the rostral ventrolateral medulla (RVL) corresponding to the location of adrenaline neurons of the C1 group (C1 area) maintain resting levels of arterial pressure (AP) and mediate the reflex cardiovascular responses to baro- and chemoreceptor activation and cerebral ischemia. The author therefore sought to determine whether neurons in the C1 area: (a) modulate regional cerebral blood flow (rCBF) and/or cerebral glucose utilization (rCGU), (b) participate in the maintenance of resting levels of CBF and CGU, and (c) mediate the CBF response to hypoxia. Rats were anesthetized, paralyzed and ventilated. The RVL was stimulated electrically or chemically, with kainic acid; lesions were placed electrolytically. rCBF was measured using 14-C-iodoantipyrine and rCGU with 14 C-2-deoxyglucose in 11 dissected brain regions

  4. Quantitative autoradiography of [3H]ouabain binding sites in rat brain

    International Nuclear Information System (INIS)

    Spyropoulos, A.C.; Rainbow, T.C.

    1984-01-01

    In vitro quantitative autoradiography was used to localize in rat brain binding sites for [ 3 H]ouabain, an inhibitor of the Na + ,K + -ATPase. High levels of [ 3 H]ouabain sites were found in the superior and inferior colliculi, the mammillary nucleus, the interpeduncular nucleus, and in various divisions of the olfactory, auditory and somatomotor systems. The heterogeneous distribution of [ 3 H]ouabain binding closely parallels the regional brain glucose consumption as determined by the [ 14 C]deoxyglucose method. Lesion studies of the rat hippocampus using the excitotoxin, ibotenic acid, showed both a marked decrease of neuronal cell types on the injected side and a corresponding decrease in [ 3 H]ouabain binding, indicating that some of the [ 3 H]ouabain binding sites are localized to neurons. The close correlation between [ 3 H]ouabain binding and regional glucose utilization provides further evidence for a linkage between glucose utilization and the neuronal Na + ,K + -ATPase. (Auth.)

  5. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  6. Energy metabolism in rat mast cells in relation to histamine secretion

    DEFF Research Database (Denmark)

    Johansen, T

    1987-01-01

    1. The relation between the energy metabolism and the secretory activity of rat peritoneal mast cells has been studied by determination of the cellular content of ATP and the rate of lactate production reflecting the rate of ATP synthesis under various experimental conditions. Secretion...... and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast...... cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48...

  7. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  8. Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

    Science.gov (United States)

    Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

    2016-11-01

    Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Functional consequences of cocaine expectation: findings in a non-human primate model of cocaine self-administration.

    Science.gov (United States)

    Porrino, Linda J; Beveridge, Thomas J R; Smith, Hilary R; Nader, Michael A

    2016-05-01

    Exposure to stimuli and environments associated with drug use is considered one of the most important contributors to relapse among substance abusers. Neuroimaging studies have identified neural circuits underlying these responses in cocaine-dependent subjects. But these studies are often difficult to interpret because of the heterogeneity of the participants, substances abused, and differences in drug histories and social variables. Therefore, the goal of this study was to assess the functional effects of exposure to cocaine-associated stimuli in a non-human primate model of cocaine self-administration, providing precise control over these variables, with the 2-[(14) C]deoxyglucose method. Rhesus monkeys self-administered 0.3 mg/kg/injection cocaine (n = 4) under a fixed-interval 3-minute (FI 3-min) schedule of reinforcement (30 injections/session) for 100 sessions. Control animals (n = 4) underwent identical schedules of food reinforcement. Sessions were then discontinued for 30 days, after which time, monkeys were exposed to cocaine- or food-paired cues, and the 2-[(14) C]deoxyglucose experiment was conducted. The presentation of the cocaine-paired cues resulted in significant increases in functional activity within highly restricted circuits that included portions of the pre-commissural striatum, medial prefrontal cortex, rostral temporal cortex and limbic thalamus when compared with control animals presented with the food-paired cues. The presentation of cocaine-associated cues increased brain functional activity in contrast to the decreases observed after cocaine consumption. Furthermore, the topography of brain circuits engaged by the expectation of cocaine is similar to the distribution of effects during the earliest phases of cocaine self-administration, prior to the onset of neuroadaptations that accompany chronic cocaine exposure. © 2015 Society for the Study of Addiction.

  10. Correlation analysis of measurement result between accelerator mass spectrometry and gamma counter

    International Nuclear Information System (INIS)

    Minamimoto, Ryogo; Cheng, C.; Oka, Takashi; Inoue, Tomio; Hamabe, Yoshimi; Shimoda, Marika

    2010-01-01

    The guidelines for microdosing in clinical trials were published in Japan in 2008 following the guidelines of the European Medicines Agency and the Food and Drug Administration. They recommend utilizing accelerator mass spectrometry (AMS) and positron emission tomography as candidates for monitoring drug metabolites in preclinical studies. We correlate the two methods by measuring appropriately labeled tissue samples from various mouse organs using both AMS and gamma counter. First, we measured the 14 C background levels in mouse organs using the AMS system. We then clarified the relationship between AMS and gamma counter by simultaneously administering 14 C-2-fluoro-2-deoxyglucose ( 14 C-FDG) and 18 F-2-fluoro-2-deoxyglucose ( 18 F-FDG). Tissue distribution was examined after 30 min, 1 h, 2 h and 4 h using the AMS system for 14 C-FDG and gamma counter for 18 F-FDG. Background 14 C levels were subtracted from the data obtained with radiotracer administration. The background 14 C concentration differed with tissue type measured. Background 14 C concentration in mouse liver was higher than in other organs, and was approximately 1.5-fold that in blood. The correlation coefficient (r) of the measurements between AMS ( 14 C-FDG) and gamma counter ( 18 F-FDG) was high in both normal (0.99 in blood, 0.91 in brain, 0.61 in liver and 0.78 in kidney) and tumor-bearing mice (0.95 in blood and 0.99 in tumor). The clearance profile of 18 F-FDG was nearly identical to that of 14 C-FDG measured with AMS. Accelerator mass spectrometry analysis has an excellent correlation with biodistribution measurements using gamma counter. Our results suggest that the combination of AMS and positron emission tomography (PET) can act as a complementary approach to accelerate drug development. (author)

  11. Medial forebrain bundle lesions fail to structurally and functionally disconnect the ventral tegmental area from many ipsilateral forebrain nuclei: implications for the neural substrate of brain stimulation reward.

    Science.gov (United States)

    Simmons, J M; Ackermann, R F; Gallistel, C R

    1998-10-15

    Lesions in the medial forebrain bundle rostral to a stimulating electrode have variable effects on the rewarding efficacy of self-stimulation. We attempted to account for this variability by measuring the anatomical and functional effects of electrolytic lesions at the level of the lateral hypothalamus (LH) and by correlating these effects to postlesion changes in threshold pulse frequency (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True Blue in the VTA and compared cell labeling patterns in forebrain regions of intact and lesioned animals. We also compared stimulation-induced regional [14C]deoxyglucose (DG) accumulation patterns in the forebrains of intact and lesioned animals. As expected, postlesion threshold shifts varied: threshold pps remained the same or decreased in eight animals, increased by small but significant amounts in three rats, and increased substantially in six subjects. Unexpectedly, LH lesions did not anatomically or functionally disconnect all forebrain nuclei from the VTA. Most septal and preoptic regions contained equivalent levels of True Blue label in intact and lesioned animals. In both intact and lesioned groups, VTA stimulation increased metabolic activity in the fundus of the striatum (FS), the nucleus of the diagonal band, and the medial preoptic area. On the other hand, True Blue labeling demonstrated anatomical disconnection of the accumbens, FS, substantia innominata/magnocellular preoptic nucleus (SI/MA), and bed nucleus of the stria terminalis. [14C]DG autoradiography indicated functional disconnection of the lateral preoptic area and SI/MA. Correlations between patterns of True Blue labeling or [14C]deoxyglucose accumulation and postlesion shifts in threshold pulse frequency were weak and generally negative. These direct measures of connectivity concord with the behavioral measures in suggesting a diffuse net-like connection between forebrain nuclei and the VTA.

  12. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  13. Cellular cardiomyoplasty for a patient with heart failure

    International Nuclear Information System (INIS)

    Zhang Fumin; Chen Yijiang; Yang Zhijian; Gao Xiang; Ma Wenzhu; Li Chuanfu; Kao, Race L.

    2003-01-01

    Background: A 73-year-old man with a history of myocardial infarction and hypertension for 5 years suffered heart failure (NYHA III-IV). Methods: 2D echo indicated hypokinesia at septal, left ventricular anterior wall and apical regions. Coronary angiograms demonstrated 60% stenosis in distal left main and 99% stenosis in proximal and distal left anterior descending coronary arteries (LAD). Both proximal artery and middle left circumflex coronary artery (LC) had 90% stenosis, and diffuse stenosis of right coronary artery (RC) was found. Myocardial perfusion imaging using 99m Tc-MIBI indicated defective perfusion of left ventricular apex, anterior wall and septal region and severe reduced perfusion of posterior inferior wall. Myocardial metabolic activities ( 18 F-deoxyglucose) also showed comparable reductions. After exposing the heart, LAD, LC, and RC were all completely occluded and bypass procedure could not be completed. Autologous satellite cells were implanted without any complication and the patient had an uneventful recovery. Results: During the first 2 months, he remained in heart failure, and by the third month, he gradually improved and reached NYHA II. At fifth month after the procedure, significant increased ejection fraction (37.1-48.6%) and wall movement with modest reduction of left ventricular systolic diameter (48-45 mm) were observed. Imaging with 18 F-deoxyglucose showed dramatic improvement in myocardial metabolic activity with similar improvement in myocardial perfusion ( 99m Tc-MIBI). Conclusion: This is the first successful case of cellular cardiomyoplasty without any conjunctional procedure for patient with severe coronary heart disease and heart failure

  14. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

    Science.gov (United States)

    Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

    2011-05-01

    Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

  15. Short Chemical Ischemia Triggers Phosphorylation of eIF2α and Death of SH-SY5Y Cells but not Proteasome Stress and Heat Shock Protein Response in both SH-SY5Y and T98G Cells.

    Science.gov (United States)

    Klacanova, Katarina; Pilchova, Ivana; Klikova, Katarina; Racay, Peter

    2016-04-01

    Both translation arrest and proteasome stress associated with accumulation of ubiquitin-conjugated protein aggregates were considered as a cause of delayed neuronal death after transient global brain ischemia; however, exact mechanisms as well as possible relationships are not fully understood. The aim of this study was to compare the effect of chemical ischemia and proteasome stress on cellular stress responses and viability of neuroblastoma SH-SY5Y and glioblastoma T98G cells. Chemical ischemia was induced by transient treatment of the cells with sodium azide in combination with 2-deoxyglucose. Proteasome stress was induced by treatment of the cells with bortezomib. Treatment of SH-SY5Y cells with sodium azide/2-deoxyglucose for 15 min was associated with cell death observed 24 h after treatment, while glioblastoma T98G cells were resistant to the same treatment. Treatment of both SH-SY5Y and T98G cells with bortezomib was associated with cell death, accumulation of ubiquitin-conjugated proteins, and increased expression of Hsp70. These typical cellular responses to proteasome stress, observed also after transient global brain ischemia, were not observed after chemical ischemia. Finally, chemical ischemia, but not proteasome stress, was in SH-SY5Y cells associated with increased phosphorylation of eIF2α, another typical cellular response triggered after transient global brain ischemia. Our results showed that short chemical ischemia of SH-SY5Y cells is not sufficient to induce both proteasome stress associated with accumulation of ubiquitin-conjugated proteins and stress response at the level of heat shock proteins despite induction of cell death and eIF2α phosphorylation.

  16. Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

    International Nuclear Information System (INIS)

    Loon, Judith van; De Ruysscher, Dirk; Wanders, Rinus; Boersma, Liesbeth; Simons, Jean; Oellers, Michel; Dingemans, Anne-Marie C.; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Teule, Jaap; Rhami, Ali; Thimister, Willy; Snoep, Gabriel; Dehing-Oberije, Cary; Lambin, Philippe

    2010-01-01

    Purpose: To evaluate the results of selective nodal irradiation on basis of 18 F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment 18 F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

  17. Nuclear medicine in childhood tumours

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    2004-01-01

    Full text: In recent years the contribution of nuclear medicine has been of increasing interest to paediatric oncology, in particular in imaging for diagnosis, staging and follow-up, in quantitative function analysis of organs at risk during oncological therapy, as well as in radionuclide therapy. For tumour imaging a great number of tumour-seeking radiopharmaceuticals are available, exploiting various metabolic and biological properties of individual tumours; several of these agents can also be applied for radionuclide therapy. More recent tracers allow the characterization of tumours, highlighting features like hormone receptors, hypoxia, MDR and apoptosis. New techniques in paediatric oncology include PET and probe-guided surgery. As a functional modality, nuclear medicine is well suited to monitor the function of organs at risk during treatment in paediatric oncology, in particular cardiac, pulmonary, renal and salivary gland function. A summary of applications and major Indications will be presented. Osteosarcoma: In differentiated osteosarcoma bone scintigraphy/SPECT using 99m Tc-diphosphonate may, as a result of Its targeting the tumour-produced osteoid, visualize not only the primary bone tumour and skeletal metastases, but also the extraosseous metastases. For preoperative therapy nd palliation of metastases beta-emitting bone-seeking agents, such as 89 Sr-chloride, 186 Re-HEDP and 153 Sm-EDTMP, are available. Lymphoma: 67 Ga-citrate has been used for decades in the detection, staging and follow up of lymphoma, as well as for early recognition of response to therapy. 201 TI-chloride scintigraphy/SPECT and PET using 18 F-deoxyglucose can also be used for this purpose. 99m Tc- sestamibi and 99m Tc-tetrofosmin are associated with p-glycoprotein, playing a role in multidrug resistance. In adults with recurrent non Hodgkin lymphoma treatment with 131 l- or 90 Y labelled anti-CD20 antibodies is highly effective. Thyroid carcinoma. 201 TI-chloride scintigraphy

  18. Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report

    International Nuclear Information System (INIS)

    Kamai, Takao; Abe, Hideyuki; Arai, Kyoko; Murakami, Satoshi; Sakamoto, Setsu; Kaji, Yasushi; Yoshida, Ken-Ichiro

    2016-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant tumor susceptibility syndrome, and the disease-related gene has been identified as fumarate hydratase (fumarase, FH). HLRCC-associated kidney cancer is an aggressive tumor characterized by early metastasis to regional lymph nodes and distant organs. Since early diagnosis and provision of definitive therapy is thought to be the best way to reduce the tumor burden, it is widely accepted that germline testing and active surveillance for an at-risk individual from a family with HLRCC is very important. However, it still remains controversial how we should treat HLRCC-associated kidney cancer. We successfully treated the patient with locally advanced HLRCC-associated kidney cancer, who has received active surveillance because of at-risk individual, by radical nephrectomy and extended retroperitoneal lymph node dissection, and examined surgically resected samples from a molecular point of view. We recommended that 13 at-risk individuals from a family with HLRCC should receive active surveillance for early detection of renal cancer. A 48-year-old woman with a left renal tumor and involvement of multiple regional lymph nodes with high accumulation of fluorine-18-deoxyglucose on positron emission tomography was treated with axitinib as a neoadjuvant therapy. Preoperative axitinib induced the shrinkage of the tumor with decreased fluorine-18-deoxyglucose accumulation. Resected samples showed two thirds tumor tissue necrosis as well as high expression of serine/threonine kinase Akt and low expression of nuclear factor E2-related factor 2 (Nrf2) which activates anti-oxidant response and protects against oxidative stress in viable cancer cells. Targeted next-generation sequencing revealed that FH mutation and loss of the second allele were completely identical between blood and tumor samples, suggesting that FH mutation plays a direct role in FH-deficient RCC. She has remained well after radical

  19. Recent aspects of thyroglobulin in physiology and pathology

    International Nuclear Information System (INIS)

    Hassane Sidibe, E.; Dangou, J.M.; Mbodj, M.

    2004-01-01

    The thyroglobulin (tg), strongly concentrated in the colloid, through a recycling to the colloid or by transcytosis to the blood stream, (function attributed to an unidentified N -Acetylglucosamine ) is linked to megalin to avoid lysosomal pathway and is delivered by a transepithelial transport (transcytosis). The promoter of this human thyroglobulin is tightly dependent on TTF-1 factor (thyroid-specific transcription factor) and Pax 8. Human recombinant TSH can increase serum baseline levels of thyroglobulin in a study from 25 to 30,000 ng/ml reflecting in part the heterogeneity of the population studied. The 131 Iodide Scan diagnosis and the measurement of serum thyroglobulin are the follow-up cornerstone that offer the opportunity in the detection of recurrence or ongoing cancer in early stage. Until now the thyroglobulin has been used in the same time than nuclear imaging. The Fluorine-18-fluoro deoxyglucose tomography positron emission plays a supplementary role in the localization of thyroid cancer recurrence sites. A control after increased post therapeutic thyroglobulin triggers a 131 Iodide scan and nuclear magnetic resonance study. In the follow-up of thyroidectomized patients with ablative radio-iodide, it is reasonable to treat patients that have an progressive increase of thyroglobulin levels but also to continue tight surveillance in those that have thyroglobulin concentrations that decrease or are stable. Fluorine-18 fluoro deoxyglucose positron emission tomography is useful in the cases with negative 131 Iodide scan and increase thyroglobulin levels. But this method has limits to find minimal disease. It is noteworthy that increased level of thyroglobulin is observed in iodine deficiency with 28.9% of world population concerned with goiter and 2% (11.2 million) with cretinism or 43 millions with mental retardation. Anti-thyroglobulin antibodies affect all the continuum of the clinical phenotype of autoimmune thyroid diseases suggesting a common

  20. Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells.

    Directory of Open Access Journals (Sweden)

    Jeanine Schibler

    Full Text Available Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266, using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog. In primary human MM samples, increased glycolytic gene expression correlated with poorer overall and event-free survival outcomes. Notably, stem-like cells showed increased mitochondrial mass, rhodamine 123 accumulation, and orthodox mitochondrial configuration while more condensed mitochondria were noted in the CD138high cells. Glycolytic inhibitor 2-deoxyglucose (2-DG induced ER stress as detected by qPCR (BiP, ATF4 and immunoblotting (BiP, CHOP and increased dihydroethidium probe oxidation both CD138low and CD138high cells. Treatment with a mitochondrial-targeting agent decyl-triphenylphosphonium (10-TPP increased intracellular steady-state pro-oxidant levels in stem-like and mature MM cells. Furthermore, 10-TPP mediated increases in mitochondrial oxidant production were suppressed by ectopic expression of manganese superoxide dismutase. Relative to 2-DG or 10-TPP alone, 2-DG plus 10-TPP combination showed increased caspase 3 activation in MM cells with minimal toxicity to the normal hematopoietic progenitor cells. Notably, treatment with polyethylene glycol conjugated catalase significantly reduced 2-DG and/or 10-TPP-induced apoptosis of MM cells. Also, the combination of 2-DG with 10-TPP decreased clonogenic survival of MM cells. Taken together, this study provides a novel strategy of metabolic oxidative stress-induced cytotoxicity of MM

  1. Recent aspects of thyroglobulin in physiology and pathology; Aspects recents de la thyroglobuline en physiologie et pathologie

    Energy Technology Data Exchange (ETDEWEB)

    Hassane Sidibe, E. [Centre Medical Marc Sankale - Fann, Dakar (Senegal); Dangou, J.M. [Laboratoire Anatomo-Pathologie, FMPO - UCAD, Dakar (Senegal); Mbodj, M. [Laboratoire de Biophysique, FMPO - UCAD, Dakar (Senegal)

    2004-06-01

    The thyroglobulin (tg), strongly concentrated in the colloid, through a recycling to the colloid or by transcytosis to the blood stream, (function attributed to an unidentified N -Acetylglucosamine ) is linked to megalin to avoid lysosomal pathway and is delivered by a transepithelial transport (transcytosis). The promoter of this human thyroglobulin is tightly dependent on TTF-1 factor (thyroid-specific transcription factor) and Pax 8. Human recombinant TSH can increase serum baseline levels of thyroglobulin in a study from 25 to 30,000 ng/ml reflecting in part the heterogeneity of the population studied. The 131 Iodide Scan diagnosis and the measurement of serum thyroglobulin are the follow-up cornerstone that offer the opportunity in the detection of recurrence or ongoing cancer in early stage. Until now the thyroglobulin has been used in the same time than nuclear imaging. The Fluorine-18-fluoro deoxyglucose tomography positron emission plays a supplementary role in the localization of thyroid cancer recurrence sites. A control after increased post therapeutic thyroglobulin triggers a 131 Iodide scan and nuclear magnetic resonance study. In the follow-up of thyroidectomized patients with ablative radio-iodide, it is reasonable to treat patients that have an progressive increase of thyroglobulin levels but also to continue tight surveillance in those that have thyroglobulin concentrations that decrease or are stable. Fluorine-18 fluoro deoxyglucose positron emission tomography is useful in the cases with negative 131 Iodide scan and increase thyroglobulin levels. But this method has limits to find minimal disease. It is noteworthy that increased level of thyroglobulin is observed in iodine deficiency with 28.9% of world population concerned with goiter and 2% (11.2 million) with cretinism or 43 millions with mental retardation. Anti-thyroglobulin antibodies affect all the continuum of the clinical phenotype of autoimmune thyroid diseases suggesting a common

  2. The present role of nuclear cardiology in clinical practice

    International Nuclear Information System (INIS)

    Clark, A.N.; Beller, G.A.

    2005-01-01

    Many advances have been made in the field of nuclear cardiology in the past decade for enhancing the diagnostic and prognostic value of stress myocardial variability using SPECT technology. Gated SPECT for determining regional and global function have provided incremental diagnostic and prognostic information in the evaluation of patients with suspected or known coronary artery disease. Left ventricular ejection fraction and regional myocardial wall thickening can now be simultaneously evaluated with regional perfusion particularly with the use of the 99m Tc-labeled perfusion agents such as sestamibi and tetrofosmin. Many studies have shown that the extent and severity of stress-induced perfusion defects have incremental prognostic value over exercise electrocardiographic stress test variables alone. Patients with normal perfusions scans have 201 Tl or with one of the 99m Tc-labeled imaging agents, or PET imaging with 18 F-deoxyglucose can accurately distinguish viable from irreversibility injured myocardium providing useful information for identifying which patients with ischemic cardiomyopathy benefit most from coronary revascularization with a subsequent improvement in left ventricular function and enhanced survival. Finally, serial stress perfusion imaging can be employed to monitor the efficacy of medical therapy that improves endothelial function and myocardial blood flow reserve

  3. AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Schjerling, Peter; Viollet, Benoit

    2008-01-01

    into muscle by certain stimuli. In contrast, no clear function has yet been determined for alpha(1) AMPK in skeletal muscle, possibly due to alpha-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H(2)O(2) stimulation to activate alpha(1) AMPK, but not alpha(2) AMPK......, in wildtype and alpha-AMPK transgenic mouse muscles, this study aimed to define conditions where alpha(1) AMPK is required to increase muscle glucose uptake. METHODOLOGY/PRINCIPAL FINDINGS: Following stimulation with H(2)O(2) (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2......-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), alpha(1) AMPK knockout or alpha(2) AMPK knockout mice. H(2)O(2) increased the activity of both alpha(1) and alpha(2) AMPK in addition to Akt phosphorylation, and H(2)O(2)-stimulated glucose...

  4. Development switch in neural circuitry underlying odor-malaise learning.

    Science.gov (United States)

    Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M

    2006-01-01

    Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

  5. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Kwee, Thomas C.; Kwee, Robert M.

    2009-01-01

    The aim of this study was to systematically review and meta-analyze published data on the diagnostic performance of combined 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of primary tumors in patients with cancer of unknown primary (CUP). A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Methodological quality of the included studies was assessed. Reported detection rates, sensitivities and specificities were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous. The 11 included studies, comprising a total sample size of 433 patients with CUP, had moderate methodological quality. Overall primary tumor detection rate, pooled sensitivity and specificity of FDG-PET/CT were 37%, 84% (95% CI 78-88%) and 84% (95% CI 78-89%), respectively. Sensitivity was heterogeneous across studies (P = 0.0001), whereas specificity was homogeneous across studies (P = 0.2114). Completeness of diagnostic workup before FDG-PET/CT, location of metastases of unknown primary, administration of CT contrast agents, type of FDG-PET/CT images evaluated and way of FDG-PET/CT review did not significantly influence diagnostic performance. In conclusion, FDG-PET/CT can be a useful method for unknown primary tumor detection. Future studies are required to prove the assumed advantage of FDG-PET/CT over FDG-PET alone and to further explore causes of heterogeneity. (orig.)

  6. PET/CT using 18-fluoro dihydroxyphenylalanine in neuroendocrine tumours according to their types

    International Nuclear Information System (INIS)

    Balogova, S.; Noskovicova, L.

    2016-01-01

    Amino acid analogue 18-fluoro dihydroxyphenylalanine (FDOPA) is a tracer of catecholamine metabolic pathway for functional imaging with positron emission tomography (PET). Diagnostic target for functional imaging of NET is a pathologically increased catecholamine or glucose metabolism or pathologically increased expression of somatostatin receptors, variably present according to type of NET. Due to heterogeneity of origin and biological properties of NET, there is no universal radiopharmaceutical permitting sufficient diagnostic accuracy of functional imaging NET of all types and of all grades of differentiation. However, the accurate staging is essential for optimal therapeutic management of NET. Diagnostic accuracy of functional nuclear medicine imaging relies upon the expression of diagnostic target by NET lesions, upon optimal choice of the tracer of diagnostic target and upon the technical performance of imaging. Commonly available comparators of FDOPA in NET are labelled somatostatin analogues for conventional scintigraphy and for PET, tracer of catecholamine synthesis and storage into secretory granules for conventional scintigraphy (123I-metaiodobenzylguanidine) and marker of glucose metabolism for PET (18-flu deoxyglucose). FDOPA shows better performances than comparators in medullary thyroid cancer, in well-differentiated catecholamine producing NETs, in well differentiated NET of mid-gut origin and in case of congenital hyperinsulinism in infants. Article summarises the documented indications of FDOPA according to type of NET and for each of them proposes currently the most performing sequence of functional imaging permitting the most accurate staging. (author)

  7. Myocardial glucose metabolism assessed by positron emission tomography and the histopathologic findings of microvessels in syndrome X

    International Nuclear Information System (INIS)

    Satake, Osamichi; Kajinami, Kouji; Ishikawa, Yoshimaro; Ueda, Tadashi; Tsugawa, Hiroichi; Kanemitsu, Seiyu; Okubo, Shinji; Takekoshi, Noboru

    2004-01-01

    Syndrome X has been recognized as a disease that is primarily reflected in the cardiac microvasculature. Myocardial metabolism in this condition has been studied, but not in relation to small vessel pathology. In order to examine the relationship between myocardial metabolism and small vessel pathology, 24 consecutive patients with syndrome X (7 men, 17 women; mean age 58 years) were evaluated by the thallium exercise stress test, positron emission tomography using F-18 fluoro-deoxyglucose (FDG), and an endomyocardial biopsy. All patients showed either diffuse or focal increase in the myocardial uptake of FDG, but only 17 patients (71%) showed hypoperfused areas with partial or complete redistribution in the thallium study. Quantification of myocardial FDG uptake revealed that the value in syndrome X patients was 10-fold higher than in controls (p<0.0001). Histopathological examination revealed that in syndrome X there is an extensive increase in smooth muscle cells and thickening of the vascular wall, even in capillary vessels, and the small vessel lumen was markedly narrowed. There was a significant inverse correlation between FDG myocardial uptake and the microvessel luminal area. In syndrome X patients, myocardial FDG uptake is increased extensively, which is strongly associated with narrowed myocardial microvasculature. (author)

  8. Characterization of non-Q wave infarction by radioisotopic methods

    International Nuclear Information System (INIS)

    Parodi, O.; Marzullo, P.; Marcassa, C.; Sambuceti, G.

    1986-01-01

    The syndrome of ''subendocardial infarction'' or ''non Q-wave infarction'', which has been defined only in terms of the presence of (ECG) electrocardiographic evidence of necrosis, has been shown to be poorly corelated with anatomical and pathomorphological findings. In a large number of patients who had been diagnosed as having this commonly described entity, the usefulness of a multiparametric approach was evaluated. The proper assessment of such patients may necessitate flow studies with T1-201, which is, however, a marker with known limitations: labelled microspheres; or Rb-82, a generator-produced positron emitter. Metabolic studies using fluoro-F-18-deoxyglucose or C-11 palmitate will defect impairment of fatty acid oxidation and residual glucose metabolism; wall motion studies will demonstrate impairment to a variable extent. The presence or absence of Q-waves does not distinguish between transmural and subendocardial infarction. The size and location of ST-T wave changes does not indicate the site of infarction. Patients with this syndrome exhibit a wide spectrum of wal motion abnormalities and usually have diffuse coronary lesions. Since conventional clinical investigations cannot be used to predict the presence and extent of necrosis, or its exact location, the studies performed should be directed toward the appropriate evaluation of perfusion and metabolic patterns. This emphasizes the important point that clinicians may investigate this syndrome by the use of the proper approach. (orig.)

  9. Myocardial metabolism, perfusion, wall motion and electrical activity in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Perloff, J.K.; Henze, E.; Schelbert, H.R.

    1982-01-01

    The cardiomyopathy of Duchenne's muscular dystrophy originates in the posterobasal left ventricle and extends chiefly to the contiguous lateral wall. Ultrastructural abnormalities in these regions precede connective tissue replacement. We postulated that a metabolic fault coincided with or antedated the subcellular abnormality. Accordingly, regional left ventricular metabolism, perfusion and wall motion were studied using positron computed tomography and metabolic isotopes supplemented by thallium perfusion scans, equilibrium radionuclide angiography and M-mode and two-dimensional echocardiography. To complete the assessment, electrocardiograms, vectorcardiograms, 24 hour taped electrocardiograms and chest x-rays were analyzed. Positron computed tomography utilizing F-18 2-fluoro 2-deoxyglucose (FDG) provided the first conclusive evidence supporting the hypothesis of a premorphologic regional metabolic fault. Thus, cardiac involvement in duchenne dystrophy emerges as a unique form of heart disease, genetically targeting specific regions of ventricular myocardium for initial metabolic and subcellular changes. Reported ultrastructural abnormalities of the impulse and conduction systems provide, at least in part, a basis for the clinically observed sinus node, intraatrial, internodal, AV nodal and infranodal disorders

  10. Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA

    International Nuclear Information System (INIS)

    Permutt, M.A.; Koranyi, L.; Keller, K.; Lacy, P.E.; Scharp, D.W.; Mueckler, M.

    1989-01-01

    Previous studies have suggested that pancreatic islet glucose transport is mediated by a high-K m , low-affinity facilitated transporter similar to that expressed in liver. To determine the relationship between islet and liver glucose transporters, liver-type glucose-transporter cDNA clones were isolated from a human liver cDNA library. The liver-type glucose-transporter cDNA clone hybridized to mRNA transcripts of the same size in human liver and pancreatic islet RNA. A cDNA library was prepared from purified human pancreatic islet tissue and screened with human liver-type glucose-transporter cDNA. The authors isolated two overlapping cDNA clones encompassing 2600 base pairs, which encode a pancreatic islet protein identical in sequence to that of the putative liver-type glucose-transporter protein. Xenopus oocytes injected with synthetic mRNA transcribed from a full-length cDNA construct exhibited increased uptake of 2-deoxyglucose, confirming the functional identity of the clone. These cDNA clones can now be used to study regulation of expression of the gene and to assess the role of inherited defects in this gene as a candidate for inherited susceptibility to non-insulin-dependent diabetes mellitus

  11. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing

    International Nuclear Information System (INIS)

    Ri, M; Tashiro, E; Oikawa, D; Shinjo, S; Tokuda, M; Yokouchi, Y; Narita, T; Masaki, A; Ito, A; Ding, J; Kusumoto, S; Ishida, T; Komatsu, H; Shiotsu, Y; Ueda, R; Iwawaki, T; Imoto, M; Iida, S

    2012-01-01

    The IRE1α-XBP1 pathway, a key component of the endoplasmic reticulum (ER) stress response, is considered to be a critical regulator for survival of multiple myeloma (MM) cells. Therefore, the availability of small-molecule inhibitors targeting this pathway would offer a new chemotherapeutic strategy for MM. Here, we screened small-molecule inhibitors of ER stress-induced XBP1 activation, and identified toyocamycin from a culture broth of an Actinomycete strain. Toyocamycin was shown to suppress thapsigargin-, tunicamycin- and 2-deoxyglucose-induced XBP1 mRNA splicing in HeLa cells without affecting activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) activation. Furthermore, although toyocamycin was unable to inhibit IRE1α phosphorylation, it prevented IRE1α-induced XBP1 mRNA cleavage in vitro. Thus, toyocamycin is an inhibitor of IRE1α-induced XBP1 mRNA cleavage. Toyocamycin inhibited not only ER stress-induced but also constitutive activation of XBP1 expression in MM lines as well as primary samples from patients. It showed synergistic effects with bortezomib, and induced apoptosis of MM cells including bortezomib-resistant cells at nanomolar levels in a dose-dependent manner. It also inhibited growth of xenografts in an in vivo model of human MM. Taken together, our results suggest toyocamycin as a lead compound for developing anti-MM therapy and XBP1 as an appropriate molecular target for anti-MM therapy

  12. Continuous spatial representations in the olfactory bulb may reflect perceptual categories

    Directory of Open Access Journals (Sweden)

    Benjamin eAuffarth

    2011-10-01

    Full Text Available In sensory processing of odors, the olfactory bulb is an important relay station, where odor representations are noise-filtered, sharpened, and possibly re-organized. An organization by perceptual qualities has been found previously in the piriform cortex, however several recent studies indicate that the olfactory bulb code reflects behaviorally relevant dimensions spatially as well as at the population level. We apply a statistical analysis on 2-deoxyglucose images, taken over the entire bulb of glomerular layer of the rat, in order to see how the recognition of odors in the nose is translated into a map of odor quality in the brain. We first confirm previous studies that the first principal component could be related to pleasantness, however the next higher principal components are not directly clear. We then find mostly continuous spatial representations for perceptual categories. We compare the space spanned by spatial and population codes to human reports of perceptual similarity between odors and our results suggest that perceptual categories could be already embedded in glomerular activations and that spatial representations give a better match than population codes. This suggests that human and rat perceptual dimensions of odorant coding are related and indicates that perceptual qualities could be represented as continuous spatial codes of the olfactory bulb glomerulus population.

  13. Complex partial seizures: cerebellar metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Theodore, W.H.; Fishbein, D.; Deitz, M.; Baldwin, P.

    1987-07-01

    We used positron emission tomography (PET) with (/sup 18/F)2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

  14. Multiparametric evaluation by simultaneous PET-MRI examination in patients with histologically proven laryngeal cancer.

    Science.gov (United States)

    Cavaliere, Carlo; Romeo, Valeria; Aiello, Marco; Mesolella, Massimo; Iorio, Brigida; Barbuto, Luigi; Cantone, Elena; Nicolai, Emanuele; Covello, Mario

    2017-03-01

    To evaluate the relationship between metabolic 18Fluoro-Deoxyglucose-Positron Emission Tomography (18FDG/PET) and morpho-functional parameters derived by Magnetic Resonance Imaging (MRI) in patients with histologically proven laryngeal cancer. To assess the clinical impact of PET/MRI examination on patient's staging and treatment planning. 16 patients with histologically proven laryngeal cancer were enrolled and underwent whole body PET/CT followed by a dedicated PET/MRI of the head/neck region. Data were separately evaluated by two blinded groups: metabolic (SUV and MTV), diffusion (ADC) and perfusion (K trans , V e , k ep and iAUC) maps were obtained by positioning regions of interest (ROIs). Tumoral local extension assessed on PET/MRI was compared to endoscopic findings. A good inter-observer agreement was found in anatomical location and local extension of PET/MRI lesions (Cohen's kappa 0.9). PET/CT SUV measures highly correlate with ones derived by PET/MRI (e.g., p=0.96 for measures on VOI). Significant correlations among metabolic, diffusion and perfusion parameters have been detected. PET/MRI had a relevant clinical impact, confirming endoscopic findings (6 cases), helping treatment planning (9 cases), and modifying endoscopic primary staging (1 case). PET/MRI is useful for primary staging of laryngeal cancer, allowing simultaneous collection of metabolic and functional data and conditioning the therapeutic strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Value of 18F-FDG PET in Clinical Staging of Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Suwen Liu; Jinming Yu; Ligang Xing

    2005-01-01

    OBJECTIVE To evaluate the feasibility of 18F-deoxyglucose positron emission tomography (18F-FDG PET) in the staging of non-small cell lung cancer(NSCLC).METHODS 105 patients with NSCLC had been examined by 18F-FDG PET before radiotherapy. The results of the 18F-FDG PET examination were compared with those of CT:RESULTS The staging was changed in 38 patients because of 18F-FDG PET findings, with PET resulting in upstaging in 31 patients and downstaging in seven patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the seven downstaged patients underwent radical surgery, among which the PET findings were concordant with the pathological findings in five patients. Distant metastasis detected by PET elevated the pre-PET stage: at stage 110.0% (2/20), stage Ⅱ 14.3% (3/21 ) and stage Ⅲ 25.0% (16/64), respectively.CONCLUSION 18F-FDG PET, by changing clinical staging in 36.2% (38/105)of NSCLC patients, has an impact on treatment strategy in NSCLC patients.

  16. Significance of 18F-FDG PET/CT imaging in the evaluation of the efficacy of lymphoma

    Institute of Scientific and Technical Information of China (English)

    CHEN Chengcheng; WANG Zhengguang; CHENG Nan

    2014-01-01

    To evaluate the 18F-labeled deoxyglucose (18F-FDG) PET/CT imaging in the evaluation of the efficacy of ly-mphoma significance.Methods:42 cases of our hospital patients with malignant lymphoma for 2-5 times 18F-FDG PET/CT imaging results in the treatment process, and the treatment process simple CT results were compared and analyzed, the final results were confirmed by pathology and clinical. Results:The lesions were found in153,including 141 malignant, benign 12, sensitivity, specificity, and accuracy evaluating of lymphoma treatment effect of 18F-FDG PET/CT were, 99.30%, 91.67%, 98.70%, were significantly better than CT examination (P

  17. Redistribution of whole-body energy metabolism by exercise. A positron emission tomography study

    International Nuclear Information System (INIS)

    Masud, M.M.; Miyake, Masayasu; Watanuki, Shoichi; Itoh, Masatoshi; Tashiro, Manabu; Fujimoto, Toshihiko

    2009-01-01

    Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using 18 F-2-fluoro-2-deoxyglucose ([ 18 F]FDG) and three-dimensional positron emission tomography (3-D PET). Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O 2 consumption (VO 2max ). [ 18 ]FDG was injected 10 min later following the exercise task. Whole-body 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P 18 F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO 2max ). The results of this investigation may contribute to sports medicine and rehabilitation science. (author)

  18. The regulation of cerebral glucose uptake and metabolism in normal and diabetic man

    International Nuclear Information System (INIS)

    Polonsky, K.

    1987-01-01

    The effects of changes in serum insulin and glucose on brain glucose metabolism using PET technology were investigated. Eight normal, right-handed, male subjects were studied on three separate occasions at least one week apart. In each subject a PET scan was performed under three different metabolic circumstances: basal conditions after an overnight fast, euglycemic clamp, and hypoglycemic clamp in which the plasma glucose was maintained at 55 mg/dl. Exogenous insulin was infused at the same rate in the euglycemic and hypoglycemic clamp studies. In the latter study, the concomitant glucose infusion rate was reduced to allow the plasma glucose concentration to fall to the desired level of mild hypoglycemia. During each study, dynamic positron emission tomography was used to characterize cerebral uptake and distribution of the Fluorine-18 2-deoxyglucose radiotracer as a function of time. Analysis of the brain uptake curve and tracer input function provided rate constants for transport and phosphorylation in accord with a 3 compartmental model (Sokoloff, 1979). Dynamic scans were performed on each study occasion allowing individual rate constants to be studied. In addition to the brain uptake curves, plasma glucose, F-18 2DG levels and counterregulatory hormone values were determined from frequent arterialized venous blood samples

  19. Basal levels of metabolic activity are elevated in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): measurement of regional activity of cytochrome oxidase and lactate dehydrogenase by histochemistry.

    Science.gov (United States)

    Dufour, Franck; Koning, Estelle; Nehlig, Astrid

    2003-08-01

    The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.

  20. Inhibition of glycolysis and growth of colon cancer cells by 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO in combination with butyrate, 2-deoxy glucose, 3-bromopyruvate or biguanides

    Directory of Open Access Journals (Sweden)

    Lea MA

    2015-09-01

    Full Text Available Introduction: Glycolysis shows a positive correlation with growth of human colon cancer cells. PFKFB3 is an important enzyme regulating glycolysis in many tumor cells and presents a target for cancer chemotherapy. We studied the action of an inhibitor of PFKFB3, 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO, as a single agent and in combination with other molecules that affect glycolysis. Materials and methods: Effects on growth were studied in four human colon cancer cell lines. Glucose metabolism was monitored by uptake from the incubation medium and lactic acid production was judged by acidification of the medium. Induction of alkaline phosphatase served as a marker of differentiation. Results: Growth of colon cancer cells was inhibited by 3PO and butyrate but only butyrate induced activation of alkaline phosphatase. Although metformin and phenformin can increase glucose metabolism, they inhibit colon cancer cell growth and can exert additive inhibitory effects in combination with 3PO. Additive growth inhibitory effects with 3PO were also observed with two compounds that inhibit glycolysis: 2-deoxyglucose and 3-bromopyruvate. Conclusion: 3PO was an inhibitor of growth of colon cancer cells and may be a useful agent in combination with other drugs that inhibit colon cancer cell proliferation.

  1. 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation.

    Science.gov (United States)

    Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

    2017-02-10

    Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis. Here we demonstrated that 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen. In vitro, BrPA facilitated the differentiation of Treg cells, suppressed Th17 cells, and inhibited the activation of DCs. These results suggested that BrPA may be a therapeutic target of murine arthritis. Although the role of IL-17 is not clarified in the treatment of RA, targeting cell metabolism to alter the immune cell functions might lead to a new therapeutic strategy for RA.

  2. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    Science.gov (United States)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  3. Effect of anesthesia on glucose production and utilization in rats

    International Nuclear Information System (INIS)

    Penicaud, L.; Ferre, P.; Kande, J.; Leturque, A.; Issad, T.; Girard, J.

    1987-01-01

    This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using [3- 3 H] glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-[1- 3 H] deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain

  4. Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

    Science.gov (United States)

    Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

    2016-01-01

    Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

  5. Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

    Science.gov (United States)

    Scheef, Lukas; Spottke, Annika; Daerr, Moritz; Joe, Alexius; Striepens, Nadine; Kölsch, Heike; Popp, Julius; Daamen, Marcel; Gorris, Dominik; Heneka, Michael T; Boecker, Henning; Biersack, Hans J; Maier, Wolfgang; Schild, Hans H; Wagner, Michael; Jessen, Frank

    2012-09-25

    To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. [¹⁸F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

  6. Hippocampal insulin microinjection and in vivo microdialysis during spatial memory testing.

    Science.gov (United States)

    McNay, Ewan C; Sandusky, Leslie A; Pearson-Leary, Jiah

    2013-01-11

    Glucose metabolism is a useful marker for local neural activity, forming the basis of methods such as 2-deoxyglucose and functional magnetic resonance imaging. However, use of such methods in animal models requires anesthesia and hence both alters the brain state and prevents behavioral measures. An alternative method is the use of in vivo microdialysis to take continuous measurement of brain extracellular fluid concentrations of glucose, lactate, and related metabolites in awake, unrestrained animals. This technique is especially useful when combined with tasks designed to rely on specific brain regions and/or acute pharmacological manipulation; for example, hippocampal measurements during a spatial working memory task (spontaneous alternation) show a dip in extracellular glucose and rise in lactate that are suggestive of enhanced glycolysis, and intrahippocampal insulin administration both improves memory and increases hippocampal glycolysis. Substances such as insulin can be delivered to the hippocampus via the same microdialysis probe used to measure metabolites. The use of spontaneous alternation as a measure of hippocampal function is designed to avoid any confound from stressful motivators (e.g. footshock), restraint, or rewards (e.g. food), all of which can alter both task performance and metabolism; this task also provides a measure of motor activity that permits control for nonspecific effects of treatment. Combined, these methods permit direct measurement of the neurochemical and metabolic variables regulating behavior.

  7. Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma

    International Nuclear Information System (INIS)

    Cremerius, U.; Zimny, M.; Bares, R.; Buell, U.; Fabry, U.; Osieka, R.; Neuerburg, J.

    2001-01-01

    Aim: To evaluate the prognostic significance of positron emission tomography (PET) using fluorine-18-[2]-fluoro-2-deoxyglucose (FDG) in patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) compared to conventional restaging (CRS). Methods: Fifty-six patients with either HD (n = 22), high-grade NHL (n = 26) or centrocytic-centroblastic NHL (n = 8) were included. PET was performed in 41 patients for treatment reevaluation up to three months after therapy and in patients with persisting residual masses (n = 10) or suspected relapse (n = 5) four to twelve months after treatment. The scans were evaluated qualitatively and quantitatively using standardised uptake values (SUV). Progression-free survival (PFS) was estimated to assess the prognostic value of FDG PET and clinical follow-up was taken as gold standard. Results: PET was positive in nineteen of 41 patients studied for treatment reevaluation. Progression was observed after a median interval of two months (range 0-15) in sixteen of 19 patients after a positive PET scan and in three of 22 patients after a negative scan (p 11.35 of lymphoma lesions was associated with poorer PFS than SUV [de

  8. Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique.

    Science.gov (United States)

    Gurung, Rit Bahadur; Gong, So Youn; Dhakal, Dipesh; Le, Tuoi Thi; Jung, Na Rae; Jung, Hye Jin; Oh, Tae Jin; Sohng, Jae Kyung

    2017-09-28

    Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4'- O -β- glucoside, curcumin 4',4''-di- O -β-glucoside, curcumin 4'- O -β-2-deoxyglucoside, and curcumin 4',4''-di- O -β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4'- O -β-glucoside and curcumin 4'- O -β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.

  9. Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.

    Science.gov (United States)

    Yu, Tao; Wang, Yong-Tao; Chen, Pan; Li, Yu-Hua; Chen, Yi-Xin; Zeng, Hang; Yu, Ai-Ming; Huang, Min; Bi, Hui-Chang

    2015-01-01

    Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. © 2015 S. Karger AG, Basel.

  10. Effects of Nicotinamide N-Methyltransferase on PANC-1 Cells Proliferation, Metastatic Potential and Survival Under Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Tao Yu

    2015-01-01

    Full Text Available Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.

  11. Analysis of the initial experience with first PET scanner and in Chile

    International Nuclear Information System (INIS)

    Massardo, Teresa; Jofre, Maria Josefina; Canessa, Jose; Gonzalez, Patricio; Humeres, Pamela; Sierralta, Paulina; Valdebenito, Robert; Galaz, Rodrigo

    2005-01-01

    The main application of positron emission tomography (PET) with Fluorine 18- deoxyglucose (FDG) is in the management of cancer patients due to the high correlation between cellular glucidic activity and malignancy. Objective: To analyze the initial group of cases performed with the first dedicated PET scanner in Chile. Method: We present the first 500 patients studied with a Siemens HR+ system using FDG produced at the Chilean Atomic Energy Commission facilities. Results: Most of the referrals were from oncology (96%). Four percent were studied due to neurological or psychiatric disorders and only 1% for myocardial viability. Lung lesions, gastrointestinal and breast carcinomas, melanoma and lymphoma corresponded to the most frequent diagnosis. Lung and lymphoma patients had clinical follow-up. There was good concordance with anatomical images and histology in those cases with available data. Fusion of FDG images with computed tomography or magnetic resonance was helpful. In a significant number of patients new tumoral sites were detected Conclusion: We confirm that in clinical practice, metabolic imaging with F18-FDG is helpful for cancer evaluation and management (au)

  12. Analysis of the initial experience with first PET scanner and in Chile

    Energy Technology Data Exchange (ETDEWEB)

    Massardo, Teresa; Jofre, Maria Josefina; Canessa, Jose; Gonzalez, Patricio; Humeres, Pamela; Sierralta, Paulina; Valdebenito, Robert; Galaz, Rodrigo [Centro PET de Imagenes Moleculares, Hospital Militar da Santiago, Santiago (Chile)

    2005-07-01

    The main application of positron emission tomography (PET) with Fluorine 18- deoxyglucose (FDG) is in the management of cancer patients due to the high correlation between cellular glucidic activity and malignancy. Objective: To analyze the initial group of cases performed with the first dedicated PET scanner in Chile. Method: We present the first 500 patients studied with a Siemens HR+ system using FDG produced at the Chilean Atomic Energy Commission facilities. Results: Most of the referrals were from oncology (96%). Four percent were studied due to neurological or psychiatric disorders and only 1% for myocardial viability. Lung lesions, gastrointestinal and breast carcinomas, melanoma and lymphoma corresponded to the most frequent diagnosis. Lung and lymphoma patients had clinical follow-up. There was good concordance with anatomical images and histology in those cases with available data. Fusion of FDG images with computed tomography or magnetic resonance was helpful. In a significant number of patients new tumoral sites were detected Conclusion: We confirm that in clinical practice, metabolic imaging with F18-FDG is helpful for cancer evaluation and management (au)

  13. Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

    Science.gov (United States)

    Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

    2017-01-01

    In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

  14. Neuron-glia metabolic coupling and plasticity.

    Science.gov (United States)

    Magistretti, Pierre J

    2006-06-01

    The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the 'astrocyte-neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron-glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

  15. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

    Science.gov (United States)

    Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

    2016-08-01

    Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Metabolic activity in striate and extrastriate cortex in the hooded rat: contralateral and ipsilateral eye input

    International Nuclear Information System (INIS)

    Thurlow, G.A.; Cooper, R.M.

    1988-01-01

    The extent of changes in glucose metabolism resulting from ipsilateral and contralateral eye activity in the posterior cortex of the hooded rat was demonstrated by means of the C-14 2-deoxyglucose autoradiographic technique. By stimulating one eye with square wave gratings and eliminating efferent activation from the other by means of enucleation or intraocular TTX injection, differences between ipsilaterally and contralaterally based visual activity in the two hemispheres were maximized. Carbon-14 levels in layer IV of autoradiographs of coronal sections were measured and combined across sections to form right and left matrices of posterior cortex metabolic activity. A difference matrix, formed by subtracting the metabolic activity matrix of cortex contralateral to the stimulated eye from the ipsilateral depressed matrix, emphasized those parts of the visual cortex that received monocular visual input. The demarcation of striate cortex by means of cholinesterase stain and the examination of autoradiographs from sections cut tangential to the cortical surface aided in the interpretation of the difference matrices. In striate cortex, differences were maximal in the medial monocular portion, and the lateral or binocular portion was shown to be divided metabolically into a far lateral contralaterally dominant strip along the cortical representation of the vertical meridian, and a more medial region of patches of more or less contralaterally dominant binocular input. Lateral peristriate differences were less than those of striate cortex, and regions of greater and lesser monocular input could be distinguished. We did not detect differences between the two hemispheres in either anterior or medial peristriate areas

  17. Present and future aspects of PET examinations

    International Nuclear Information System (INIS)

    Inoue, Tomio

    2003-01-01

    The PET examination gives the body distribution image of a compound labeled with the positron emitter manufactured by cyclotron. Recently, PET with F18-deoxyglucose (FDG) attracts considerable attention because the imaging is particularly useful for cancer detection. Since the technique was authorized by the United States (US) official health insurance in 1998, the number of the examination is increasing, which is also under similar situation in Japan due to the latest partial authorization for some malignant tumors. In Japan, about 30,000 examinations per year are carried out, half of which, in private hospitals. Their purpose is increasingly for cancer detection. For future PET examination, awaited are improvement of PET camera and development of a novel imaging agent. PET/CT imaging is for the former and F18-α-methyltyrosine, for the latter. Miniaturization of cyclotron, FDG delivery system, improved FDG synthetic method, popularization of PET/CT, development of PET camera for health examination, clinical trial of a novel imaging agent, and spread of PET health examination and operation of PET Center, are expected for future progress of PET technique. (N.I.)

  18. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    Science.gov (United States)

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer.

    Science.gov (United States)

    Momcilovic, Milica; Bailey, Sean T; Lee, Jason T; Fishbein, Michael C; Magyar, Clara; Braas, Daniel; Graeber, Thomas; Jackson, Nicholas J; Czernin, Johannes; Emberley, Ethan; Gross, Matthew; Janes, Julie; Mackinnon, Andy; Pan, Alison; Rodriguez, Mirna; Works, Melissa; Zhang, Winter; Parlati, Francesco; Demo, Susan; Garon, Edward; Krysan, Kostyantyn; Walser, Tonya C; Dubinett, Steven M; Sadeghi, Saman; Christofk, Heather R; Shackelford, David B

    2017-01-17

    Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) and 11 C-glutamine ( 11 C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18 F-FDG and 11 C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer

    Directory of Open Access Journals (Sweden)

    Milica Momcilovic

    2017-01-01

    Full Text Available Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR mutant non-small cell lung cancer (NSCLC as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK pathway in EGFR (del19 lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET imaging with 18F-fluoro-2-deoxyglucose (18F-FDG and 11C-glutamine (11C-Gln of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy.

  1. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

    Science.gov (United States)

    Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

    2008-02-01

    To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

  2. Semiquantitative analysis of interictal glucose metabolism between generalized epilepsy and localization related epilepsy

    International Nuclear Information System (INIS)

    Hikima, Akio; Mochizuki, Hiroyuki; Oriuchi, Noboru; Endo, Keigo; Morikawa, Akihiro

    2004-01-01

    Positron emission tomography (PET) with [ 18 F]fluoro-D-deoxyglucose (FDG) has been used to detect seizure foci and evaluate surgical resection with localization related epilepsies. However, few investigations have focused on generalized epilepsy in children. To reveal the pathophysiology of generalized epilepsy, we studied 11 patients with generalized epilepsy except West syndrome, and 11 patients with localization related epilepsy without organic disease. The FDG PET was performed by simultaneous emission and transmission scanning. We placed regions of interest (ROI) on bilateral frontal lobe, parietal lobe, occipital lobe, temporal lobe, basal ganglia, thalamus and cerebellum. Standardized uptake value (SUV) was measured and normalized to SUV of ipsilateral cerebellum. Then, we compared the data of generalized epilepsy to those of localization related epilepsy. FDG PET revealed significant interictal glucose hypometabolism in bilateral basal ganglia in generalized epilepsy compared to that in localization related epilepsy (right side: p=0.0095, left side: p=0.0256, Mann-Whitney test). No other region showed any significant difference (p>0.05) between the two groups. These findings indicate that the basal ganglia is involved in the outbreak of generalized seizures or is affected secondarily by the epileptogenicity itself. (author)

  3. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    International Nuclear Information System (INIS)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa; Takeyama, Daiya; Yamane, Yuriko; Chida, Masanobu; Otani, Hiroki; Shirato, Kunio; Ido, Tatsuo.

    1997-01-01

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18 F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6±1.6 vs. 4.1±0.5, p<0.01) and posterolateral wall (5.9±0.7 vs. 3.8±0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  4. The Absolute Standardization Method of 18F by Using 4π(PC)-γ Coincidence Counting System

    International Nuclear Information System (INIS)

    Pujadi

    2003-01-01

    The absolute standardization of 18 F radionuclide had been carried out using 4π(PC)-γ coincidence counting. The radionuclide 18 F fluoro 2 deoxyglucose (FDG) was the quantity used at nuclear medicine in diagnosis of oncology. The radionuclide 18 F had been produced by 18 O(p,n) 18 F reaction in a cyclotron. Source preparation had been done by gravimetry method after source was dissolved in aquadest. The samples have been measured using 4π(PC)-γ coincidence counting on different three window gamma energy, the gamma windows were set on 511 keV peak, 1022 keV and above 511 keV region. The result of measurement on 1022 keV peak and above 511 keV region, are fairly good with discrepancy about 0.15%, but the linearity of gamma window above 511 keV is the best with R 2 = 0.8287. The measurement on 511 keV gamma window region gave the result with difference 2.28% compared with another two region. (author)

  5. Dose-response study of caffeine effects on cerebral functional activity with a specific focus on dependence.

    Science.gov (United States)

    Nehlig, A; Boyet, S

    2000-03-06

    Caffeine is a behavioral stimulant consumed on a worldwide basis. The question of whether caffeine is addictive has been debated for over a decade. Caffeine acts as a mild positive reinforcer but is not consistently self-administered in humans or animals. With [14C]2-deoxyglucose autoradiography, we studied the effects of increasing doses of caffeine on cerebral glucose utilization in rats. At 1 mg/kg, caffeine activated the caudate nucleus mediating locomotion, and the raphe nuclei and locus coeruleus involved with mood and sleep. After 2.5 and 5 mg/kg caffeine, metabolic activation spread to other components of the nigrostriatal dopaminergic system, the thalamus, ventral tegmental area and amygdala. The functional activation of the shell of the nucleus accumbens, an area involved in addiction and reward, was only induced by the highest dose of caffeine, 10 mg/kg. At this dose, the activation of the shell of the nucleus accumbens occurred together with that of the core of the nucleus accumbens and of most other brain regions. These data correlate well with the known sensitivity of locomotion, mood and sleep to low doses of caffeine. They also show that low doses of caffeine which reflect the usual human level of consumption fail to activate reward circuits in the brain and thus provide functional evidence of the very low addictive potential of caffeine.

  6. Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

    Science.gov (United States)

    Mayberg, H S; Sadzot, B; Meltzer, C C; Fisher, R S; Lesser, R P; Dannals, R F; Lever, J R; Wilson, A A; Ravert, H T; Wagner, H N

    1991-07-01

    Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

  7. Polyphenol Stilbenes from Fenugreek (Trigonella foenum-graecum L. Seeds Improve Insulin Sensitivity and Mitochondrial Function in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Gang Li

    2018-01-01

    Full Text Available Fenugreek (Trigonella foenum-graecum L. is a well-known annual plant that is widely distributed worldwide and has possessed obvious hypoglycemic and hypercholesterolemia characteristics. In our previous study, three polyphenol stilbenes were separated from fenugreek seeds. Here, we investigated the effect of polyphenol stilbenes on adipogenesis and insulin resistance in 3T3-L1 adipocytes. Oil Red O staining and triglyceride assays showed that polyphenol stilbenes differently reduced lipid accumulation by suppressing the expression of adipocyte-specific proteins. In addition, polyphenol stilbenes improved the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino-2-deoxyglucose (2-NBDG by promoting the phosphorylation of protein kinase B (AKT and AMP-activated protein kinase (AMPK. In present studies, it was found that polyphenol stilbenes had the ability to scavenge reactive oxygen species (ROS. Results from adenosine triphosphate (ATP production and mitochondrial membrane potentials suggested that mitochondria play a critical role in insulin resistance and related signaling activation, such as AKT and AMPK. Rhaponticin, one of the stilbenes from fenugreek, had the strongest activity among the three compounds in vitro. Future studies will focus on mitochondrial biogenesis and function.

  8. Hardware and software design considerations in engineering an image processing workstation

    International Nuclear Information System (INIS)

    Feingold, E.; Seshadri, S.B.; Tretiak, O.J.

    1986-01-01

    The use of densitometry in autoradiography is not novel, but computer-assisted video densitometry is gaining increasing popularity. This is because functional mapping with radionuclides, such as the 2-deoxyglucose (2-DG) technique, produces enormous numbers of images which require quite detailed analysis and quantification. Effective use of the data contained in 2-DG autoradiograms is almost unfeasible if computer assisted image analysis is not utilized, and a video densitometric system (one that uses a television camera to scan the autoradiogram) is both suitable and economical. This paper will describe the software and hardware design and implementation of one such image analysis system: the DUMAs system and the BRAIN software package. This chapter describes the results of the authors' development effort. Since the user interface is paramount, the next section describes the BRAIN software. In the following section, they describe the issues relevant to selecting the DUMAS hardware and some of the alternatives considered. In the concluding section, they summarize the status of the DUMAS/BRAIN project and look at future developments

  9. Zinc uptake in vitro by human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Newsome, D.A.; Rothman, R.J.

    1987-01-01

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied 65 Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM 65 Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM 65 Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of 65 Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to 65 Zn retained approximately 70% of accumulated 65 Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of 65 Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc

  10. Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy.

    Directory of Open Access Journals (Sweden)

    De-Hua Yu

    Full Text Available We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (approximately 10 fold. It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor, but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.

  11. Hungry Neurons: Metabolic Insights on Seizure Dynamics

    Directory of Open Access Journals (Sweden)

    Paolo Bazzigaluppi

    2017-10-01

    Full Text Available Epilepsy afflicts up to 1.6% of the population and the mechanisms underlying the appearance of seizures are still not understood. In past years, many efforts have been spent trying to understand the mechanisms underlying the excessive and synchronous firing of neurons. Traditionally, attention was pointed towards synaptic (dysfunction and extracellular ionic species (dysregulation. Recently, novel clinical and preclinical studies explored the role of brain metabolism (i.e., glucose utilization of seizures pathophysiology revealing (in most cases reduced metabolism in the inter-ictal period and increased metabolism in the seconds preceding and during the appearance of seizures. In the present review, we summarize the clinical and preclinical observations showing metabolic dysregulation during epileptogenesis, seizure initiation, and termination, and in the inter-ictal period. Recent preclinical studies have shown that 2-Deoxyglucose (2-DG, a glycolysis blocker is a novel therapeutic approach to reduce seizures. Furthermore, we present initial evidence for the effectiveness of 2-DG in arresting 4-Aminopyridine induced neocortical seizures in vivo in the mouse.

  12. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  13. Generation of a glucose de-repressed mutant of Trichoderma reesei using disparity mutagenesis.

    Science.gov (United States)

    Iwakuma, Hidekazu; Koyama, Yoshiyuki; Miyachi, Ayako; Nasukawa, Masashi; Matsumoto, Hitoshi; Yano, Shuntaro; Ogihara, Jun; Kasumi, Takafumi

    2016-01-01

    We obtained a novel glucose de-repressed mutant of Trichoderma reesei using disparity mutagenesis. A plasmid containing DNA polymerase δ lacking proofreading activity, and AMAI, an autonomously replicating sequence was introduced into T. reesei ATCC66589. The rate of mutation evaluated with 5-fluoroorotic acid resistance was approximately 30-fold higher than that obtained by UV irradiation. The transformants harboring incompetent DNA polymerase δ were then selected on 2-deoxyglucose agar plates with hygromycin B. The pNP-lactoside hydrolyzing activities of mutants were 2 to 5-fold higher than the parent in liquid medium containing glucose. Notably, the amino acid sequence of cre1, a key gene involved in glucose repression, was identical in the mutant and parent strains, and further, the cre1 expression levels was not abolished in the mutant. Taken together, these results demonstrate that the strains of T. reesei generated by disparity mutagenesis are glucose de-repressed variants that contain mutations in yet-unidentified factors other than cre1.

  14. Safety of dose escalation by simultaneous integrated boosting radiation dose within the primary tumor guided by 18FDG-PET/CT for esophageal cancer

    International Nuclear Information System (INIS)

    Yu, Wen; Cai, Xu-Wei; Liu, Qi; Zhu, Zheng-Fei; Feng, Wen; Zhang, Qin; Zhang, Ying-Jian; Yao, Zhi-Feng; Fu, Xiao-Long

    2015-01-01

    Purpose: To observe the safety of selective dose boost to the pre-treatment high 18 F-deoxyglucose (FDG) uptake areas of the esophageal GTV. Methods: Patients with esophageal squamous cell carcinoma were treated with escalating radiation dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment 50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade 3 or higher acute toxicities causing continuous interruption of radiation for over 1 week. Results: From April 2012 to February 2014, dose has been escalated up to LEVEL 4 (70 Gy). All of the 25 patients finished the prescribed dose without DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2 died of esophageal hemorrhage within 1 month after completion of radiotherapy, which was not definitely correlated with treatment yet. Late toxicities remained under observation. With median follow up of 8.9 months, one-year overall survival and local control was 69.2% and 77.4%, respectively. Conclusions: Dose escalation in esophageal cancer based on 18 FDG-PET/CT has been safely achieved up to 70 Gy using the SIB technique. Acute toxicities were well tolerated, whereas late toxicities and long-term outcomes deserved further observation

  15. Growth and ethanol fermentation ability on hexose and pentose sugars and glucose effect under various conditions in thermotolerant yeast Kluyveromyces marxianus.

    Science.gov (United States)

    Rodrussamee, Nadchanok; Lertwattanasakul, Noppon; Hirata, Katsushi; Suprayogi; Limtong, Savitree; Kosaka, Tomoyuki; Yamada, Mamoru

    2011-05-01

    Ethanol fermentation ability of the thermotolerant yeast Kluyveromyces marxianus, which is able to utilize various sugars including glucose, mannose, galactose, xylose, and arabinose, was examined under shaking and static conditions at high temperatures. The yeast was found to produce ethanol from all of these sugars except for arabinose under a shaking condition but only from hexose sugars under a static condition. Growth and sugar utilization rate under a static condition were slower than those under a shaking condition, but maximum ethanol yield was slightly higher. Even at 40°C, a level of ethanol production similar to that at 30°C was observed except for galactose under a static condition. Glucose repression on utilization of other sugars was observed, and it was more evident at elevated temperatures. Consistent results were obtained by the addition of 2-deoxyglucose. The glucose effect was further examined at a transcription level, and it was found that KmGAL1 for galactokinase and KmXYL1 for xylose reductase for galactose and xylose/arabinose utilization, respectively, were repressed by glucose at low and high temperatures, but KmHXK2 for hexokinase was not repressed. We discuss the possible mechanism of glucose repression and the potential for utilization of K. marxianus in high-temperature fermentation with mixed sugars containing glucose.

  16. A Hierarchical Bayesian Model for the Identification of PET Markers Associated to the Prediction of Surgical Outcome after Anterior Temporal Lobe Resection

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    Sharon Chiang

    2017-12-01

    Full Text Available We develop an integrative Bayesian predictive modeling framework that identifies individual pathological brain states based on the selection of fluoro-deoxyglucose positron emission tomography (PET imaging biomarkers and evaluates the association of those states with a clinical outcome. We consider data from a study on temporal lobe epilepsy (TLE patients who subsequently underwent anterior temporal lobe resection. Our modeling framework looks at the observed profiles of regional glucose metabolism in PET as the phenotypic manifestation of a latent individual pathologic state, which is assumed to vary across the population. The modeling strategy we adopt allows the identification of patient subgroups characterized by latent pathologies differentially associated to the clinical outcome of interest. It also identifies imaging biomarkers characterizing the pathological states of the subjects. In the data application, we identify a subgroup of TLE patients at high risk for post-surgical seizure recurrence after anterior temporal lobe resection, together with a set of discriminatory brain regions that can be used to distinguish the latent subgroups. We show that the proposed method achieves high cross-validated accuracy in predicting post-surgical seizure recurrence.

  17. Use of osmolytes during solubilization and reconstitution of phosphate: sugar phosphate antiport from bacteria

    International Nuclear Information System (INIS)

    Ambudkar, S.V.; Sonna, L.A.; Maloney, P.C.

    1986-01-01

    Phosphate:2-deoxyglucose 6-phosphate (Pi:2DG6P) antiport was extracted from Streptococcus lactis or Staphylococcus aureus with 1.1% octylglucoside in the presence of 0.37% E. coli lipid and reconstituted by detergent dilution. Because previous work suggested inactivation at an early stage, the authors introduced protein stabilants during solubilization. When 20% glycerol was used, proteoliposomes showed a 20-fold increase in 32 Pi transport. This enhanced recovery required phospholipid plus glycerol, and was found only when both were added together with the detergent. Glycerol protection yielded proteoliposomes in which antiporters retained their normal kinetic properties, and Pi exchange by the streptococcal example gave a maximal rate (200-400 nmol/min per mg protein) and a turnover number (30-50/s) which suggested that inactivation had been avoided. Further study showed that 20% glycerol could be replaced by equally high concentrations of compounds classified as osmolytes polyols (erythritol, xylitol, sorbitol), sugars (glucose, trehalose) and certain amino acids (glycine, proline, but not valine). The authors suggest that osmolytes may be used to fully stabilize chemiosmotic transporters during reconstitution

  18. Greater ATP dependence than sodium dependence of radiocalcium efflux in bullfrog ventricle

    International Nuclear Information System (INIS)

    Brommundt, G.; Kavaler, F.

    1985-01-01

    45 Ca efflux was studied in intact bullfrog ventricles following a 2-h period of loading with radiocalcium-containing Ringer solution. The cannulated ventricle was placed in a closed air-filled container to which were applied rhythmic, electronically timed, positive- and negative-pressure pulsations, which induced ventricular volume excursions. The mechanical arrangement and timing circuitry made it possible for each period to be as short in duration as 15 s. By use of this technique, penetration of the extracellular space by [ 14 C]inulin was found to be complete within 30 s, and recovery of the inulin proceeded with a time constant of 17-24 s, indicating a completeness of recovery of 98% within 90 s. Washout of added 45 Ca was quantitatively quite close to that of inulin, and in addition the estimated rate of sequestration of the isotope was slow enough to introduce only a small error into the experimental results. 45 Ca efflux was only slightly (15%) sensitive to replacement of extracellular sodium but was profoundly sensitive to the inhibitors of ATP synthesis, cyanide and 2-deoxy-glucose

  19. Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

    Science.gov (United States)

    Eschbach, Ralf S.; Fendler, Wolfgang P.; Kazmierczak, Philipp M.; Hacker, Marcus; Rominger, Axel; Carlsen, Janette; Hirner-Eppeneder, Heidrun; Schuster, Jessica; Moser, Matthias; Havla, Lukas; Schneider, Moritz J.; Ingrisch, Michael; Spaeth, Lukas; Reiser, Maximilian F.; Nikolaou, Konstantin; Cyran, Clemens C.

    2015-01-01

    Objectives To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation. Materials and Methods Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group) female athymic nude rats (Hsd:RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV, %) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67). Results Regorafenib significantly (pregorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F-FDG-PET validated by immunohistochemistry. PMID:25668193

  20. Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Yoojoo Lim

    Full Text Available Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear.Tumor attenuation as measured by Hounsfield units (HU in contrast-enhanced computed tomography (CT and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80 treated with regorafenib in a prospective study.141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%-20.7%. Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002. Among 53 patients with lung metastases, 17 (32.1% developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50 and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13.Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies.

  1. Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer

    Science.gov (United States)

    Yoon, Jeong Hee; Lee, Jeong Min; Lee, Jung Min; Paeng, Jin Chul; Won, Jae-Kyung; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Lee, Kyung-Hun; Kim, Jee Hyun; Kim, Tae-You

    2015-01-01

    Background Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear. Methods Tumor attenuation as measured by Hounsfield units (HU) in contrast-enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study. Results 141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%–20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson’s r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13). Conclusion Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies. PMID:26671465

  2. Physiological Study of Lactobacillus delbrueckii subsp. bulgaricus Strains in a Novel Chemically Defined Medium

    Science.gov (United States)

    Chervaux, Christian; Ehrlich, S. Dusko; Maguin, Emmanuelle

    2000-01-01

    We developed a chemically defined medium called milieu proche du lait (MPL), in which 22 Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) strains exhibited growth rates ranging from 0.55 to 1 h−1. MPL can also be used for cultivation of other lactobacilli and Streptococcus thermophilus. The growth characteristics of L. bulgaricus in MPL containing different carbon sources were determined, including an initial characterization of the phosphotransferase system transporters involved. For the 22 tested strains, growth on lactose was faster than on glucose, mannose, and fructose. Lactose concentrations below 0.4% were limiting for growth. We isolated 2-deoxyglucose-resistant mutants from strains CNRZ397 and ATCC 11842. CNRZ397-derived mutants were all deficient for glucose, fructose, and mannose utilization, indicating that these three sugars are probably transported via a unique mannose-specific-enzyme-II-like transporter. In contrast, mutants of ATCC 11842 exhibited diverse phenotypes, suggesting that multiple transporters may exist in that strain. We also developed a protein labeling method and verified that exopolysaccharide production and phage infection can occur in MPL. The MPL medium should thus be useful in conducting physiological studies of L. bulgaricus and other lactic acid bacteria under well controlled nutritional conditions. PMID:11097906

  3. A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway.

    Science.gov (United States)

    Cheraghchi-Bashi, Azadeh; Parker, Christine A; Curry, Ed; Salazar, Jean-Frederic; Gungor, Hatice; Saleem, Azeem; Cunnea, Paula; Rama, Nona; Salinas, Cristian; Mills, Gordon B; Morris, Shannon R; Kumar, Rakesh; Gabra, Hani; Stronach, Euan A

    2015-12-08

    Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum.

  4. Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-{sup 19}F-NMR

    Energy Technology Data Exchange (ETDEWEB)

    Dickinson, Elizabeth, E-mail: elizabeth.dickinson@york.ac.uk [University of York, Department of Chemistry (United Kingdom); Arnold, John R. P. [Selby College (United Kingdom); Fisher, Julie [University of Leeds, School of Chemistry (United Kingdom)

    2017-02-15

    The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using {sup 19}F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.

  5. Measurement of temporal asymmetries of glucose consumption using linear profiles: reproducibility and comparison with visual analysis

    International Nuclear Information System (INIS)

    Matheja, P.; Kuwert, T.; Schaefers, M.; Schaefers, K.; Schober, O.; Diehl, B.; Stodieck, S.R.G.; Ringelstein, E.B.; Schuierer, G.

    1998-01-01

    The aim of our study was to test the reproducibility of this method and to compare its diagnostic performance to that of visual analysis in patients with complex partial seizures (CPS). Regional cerebral glucose consumption (rCMRGLc) was measured interictally in 25 CPS patients and 10 controls using F-18-deoxyglucose and the positron emission tomography (PET) camera ECAT EXACT 47. The PET scans were visually analyzed for the occurrence of unilateral temporal hypometabolism. Furthermore, rCMRGLc was quantified on six contiguous coronal planes by manually tracing maximal values of temporal glucose consumption, thus creating line profiles of temporal glucose consumption for each side. Indices of asymmetry (ASY) were then calculated from these line profiles in four temporal regions and compared to the corresponding 95% confidence intervals of the control data. All analyses were performed by two observers independently from each other and without knowledge of the clinical findings. The agreement between the two observers with regard to focus lateralization was 96% on visual analysis and 100% on quantitative analysis. There was an excellent agreement with regard to focus lateralization between visual and quantitative evaluation. (orig.) [de

  6. Tributyltin Differentially Promotes Development of a Phenotypically Distinct Adipocyte

    Science.gov (United States)

    Regnier, Shane M.; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L.; Sargis, Robert M.

    2015-01-01

    Objective Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being pro-adipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. Methods The co-stimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. Results TBT enhanced expression of the adipocyte marker C/EBPα with co-exposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of co-treatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. Conclusions TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. PMID:26243053

  7. Tributyltin differentially promotes development of a phenotypically distinct adipocyte.

    Science.gov (United States)

    Regnier, Shane M; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L; Sargis, Robert M

    2015-09-01

    Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being proadipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. The costimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. TBT enhanced expression of the adipocyte marker C/EBPα with coexposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of cotreatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. © 2015 The Obesity Society.

  8. Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

    2017-09-06

    The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P system (P skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

  9. Neural correlates of sensorimotor gating: A metabolic positron emission tomography study in awake rats

    Directory of Open Access Journals (Sweden)

    Cathrin eRohleder

    2014-05-01

    Full Text Available Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET. Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during passive PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.

  10. Effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J.J.; McCulloch, J.

    1983-02-01

    The effects of the dopaminergic agonist apomorphine upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine effected significant increases in glucose utilization in 15 regions of the CNS, and significant reductions in glucose utilization in two regions of the CNS. In rats anesthetized with chloral hydrate, the effects of apomorphine upon local glucose utilization were less widespread and less marked than in conscious animals. The profound effects of chloral hydrate anesthesia upon local cerebral glucose use, and the modification by this anesthetic regime of the local metabolic responses to apomorphine, emphasize the difficulties which exists in the extrapolation of data from anesthetized animals to the conditions which prevail in the conscious animal.

  11. Increases in the numerical density of GAT-1 positive puncta in the barrel cortex of adult mice after fear conditioning.

    Directory of Open Access Journals (Sweden)

    Ewa Siucinska

    Full Text Available Three days of fear conditioning that combines tactile stimulation of a row of facial vibrissae (conditioned stimulus, CS with a tail shock (unconditioned stimulus, UCS expands the representation of "trained" vibrissae, which can be demonstrated by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also shown that functional reorganization of the primary somatosensory cortex (S1 increases GABAergic markers in the hollows of "trained" barrels of the adult mouse. This study investigated how whisker-shock conditioning (CS+UCS affected the expression of puncta of a high-affinity GABA plasma membrane transporter GAT-1 in the barrel cortex of mice 24 h after associative learning paradigm. We found that whisker-shock conditioning (CS+UCS led to increase expression of neuronal and astroglial GAT-1 puncta in the "trained" row compared to controls: Pseudoconditioned, CS-only, UCS-only and Naïve animals. These findings suggest that fear conditioning specifically induces activation of systems regulating cellular levels of the inhibitory neurotransmitter GABA.

  12. Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1.

    Science.gov (United States)

    Ros, Raquel; Gómez Garre, Pilar; Hirano, Michio; Tai, Yen F; Ampuero, Israel; Vidal, Lídice; Rojo, Ana; Fontan, Aurora; Vazquez, Ana; Fanjul, Samira; Hernandez, Jaime; Cantarero, Susana; Hoenicka, Janet; Jones, Alison; Ahsan, R Laila; Pavese, Nicola; Piccini, Paola; Brooks, David J; Perez-Tur, Jordi; Nyggard, Torbjorn; de Yébenes, Justo G

    2005-05-01

    Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the areas of interest with additional markers. The disease status was defined according to the clinical and positron emission tomography data. We excluded linkage to the tau gene in chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area contains at least three genes, whose relevance in PSP is unknown. We expect to further define the gene responsible for PSP, which could help to understand the pathogenesis of this disease and to design effective treatment.

  13. Steviol glycosides in purified stevia leaf extract sharing the same metabolic fate.

    Science.gov (United States)

    Purkayastha, Sidd; Markosyan, Avetik; Prakash, Indra; Bhusari, Sachin; Pugh, George; Lynch, Barry; Roberts, Ashley

    2016-06-01

    The safety of steviol glycosides is based on data available on several individual steviol glycosides and on the terminal absorbed metabolite, steviol. Many more steviol glycosides have been identified, but are not yet included in regulatory assessments. Demonstration that these glycosides share the same metabolic fate would indicate applicability of the same regulatory paradigm. In vitro incubation assays with pooled human fecal homogenates, using rebaudiosides A, B, C, D, E, F and M, as well as steviolbioside and dulcoside A, at two concentrations over 24-48 h, were conducted to assess the metabolic fate of various steviol glycoside classes and to demonstrate that likely all steviol glycosides are metabolized to steviol. The data show that glycosidic side chains containing glucose, rhamnose, xylose, fructose and deoxy-glucose, including combinations of α(1-2), β-1, β(1-2), β(1-3), and β(1-6) linkages, were degraded to steviol mostly within 24 h. Given a common metabolite structure and a shared metabolic fate, safety data available for individual steviol glycosides can be used to support safety of purified steviol glycosides in general. Therefore, steviol glycosides specifications adopted by the regulatory authorities should include all steviol glycosides belonging to the five groups of steviol glycosides and a group acceptable daily intake established. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. When vision guides movement: a functional imaging study of the monkey brain.

    Science.gov (United States)

    Gregoriou, Georgia G; Savaki, Helen E

    2003-07-01

    Goal-directed reaching requires a precise neural representation of the arm position and the target location. Parietal and frontal cortical areas rely on visual, somatosensory, and motor signals to guide the reaching arm to the desired position in space. To dissociate the regions processing these signals, we applied the quantitative [(14)C]-deoxyglucose method on monkeys reaching either in the light or in the dark. Nonvisual (somatosensory and memory-related) guidance of the arm, during reaching in the dark, induced activation of discrete regions in the parietal, premotor, and motor cortices. These included the dorsal part of the medial bank of the intraparietal sulcus, the ventral premotor area F4, the dorsal premotor area F2 below the superior precentral dimple, and the primary somatosensory and motor cortices. Additional parietal and premotor regions comprising the ventral intraparietal cortex, ventral premotor area F5, and the ventral part of dorsal premotor area F2 were activated by visual guidance of the arm during reaching in the light. This study provides evidence that different regions of the parieto-premotor circuit process the visual, somatosensory, and motor-memory-related signals which guide the moving arm.

  15. PET with a dual-head coincidence gamma camera in head and neck cancer: A comparison with computed tomography and dedicated PET

    International Nuclear Information System (INIS)

    Zimny, M.

    2001-01-01

    Positron emission tomography with 18 F-fluoro-deoxyglucose (FDG PET) is a promising imaging tool for detecting and staging of primary or recurrent head and neck cancer. The aim of this study was to evaluate a dual-head gamma camera modified for coincidence detection (KGK-PET) in comparison to computed tomography (CT) and dedicated PET (dPET). 50 patients with known or suspected primary or recurrent head and neck cancer were enrolled. 32 patients underwent KGK-PET and dPET using a one-day protocol. The sensitivity for the detection of primary/ recurrent head and neck cancer for KGK-PET and CT was 80% and 54%, respectively, specificity was 73% and 82%, respectively. The sensitivity and specificity for the detection of lymph node metastases based on neck sides with KGK-PET was 71% (CT: 65%) and 88% (CT: 89%) respectively. In comparison to dPET, KGK-PET revealed concordant results in 32/32 patients with respect to primary tumor/recurrent disease and in 55/60 evaluated neck sides. All involved neck sides that were missed by KGK-PET were also negative with dPET. These results indicate that in patients with head and neck cancer KGK-PET reveals information, that are similar to dPET and complementary to CT. (orig.) [de

  16. Anatomo-radiological correlation using 18-FDG-PET in abdominal sepsis model in rats: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Italo Medeiros; Carvalho, Marilia Daniela Ferreira; Nascimento, Rafael Pereira; Macedo, Robson; Aquino, Monica Raquel de Souza; Medeiros, Aldo Cunha, E-mail: cirurgex.ufrn@gmail.com [Universidade Federal do Rio Grande do Norte (UFRN), Natal (Brazil)

    2017-03-15

    Purpose: To examine a correlation of micro-PET images with photographic images of the digestive organs in abdominal sepsis model. Methods: Male Wistar rats weighing 265±18g were used. Abdominal sepsis was induced by ligature and cecal puncture. Micro-PET Images from abdominal cavity septic foci were obtained using 18-Fluoro-deoxyglucose, looking for a correlation with photographic images of abdominal cavity organs. Pearson's correlation test was used. Results: The mean standard uptake values (SUV) and lesion areas were 2.58±0.63SUVbwg/ml and 546.87±300.95mm{sup 2} , respectively. There was a strong positive correlation between the two variables (r=0.863, p=0.137), which resulted in a coefficient of determination r{sup 2} ≅0.75, meaning that 75% of SUV variation is explained by the lesion areas of digestive organs. Conclusion: Micro-PET allows high throughput assessment of lesion count and volume in pre-clinical rat model of CPL abdominal sepsis. (author)

  17. Fluorine-18 fluoro-2-deozyglucose positron emission tomography in recurrent rectal cancer: relation to tumour size and cellularity

    International Nuclear Information System (INIS)

    Ito, Kengo; Kato, Takashi; Ohta, Tyohiro; Tadokoro, Masanori; Yamada, Tetsuya; Ikeda, Mitsuru; Nishino, Masanari; Ishigaki, Takeo; Ito, Katsuiki; Gambhir, S.

    1996-01-01

    The aim of this study was to assess the value of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography in patients with recurrent rectal cancer, in relation to tumour size and cellularity. Thirty-seven patients (21 mean and 16 women; mean age, 55.4±9.58 years) with suspected recurrence of rectal cancer were studied. FDG uptake was quantified by the differential absorption ratio (DAR). In 29 patients magnetic resonance imaging was also performed. To evaluate the signal intensity of the lesion, the lesion to muscle signal intensity ratio (SIR) were calculated on T2-weighted images. In seven patients who received surgical treatment the DAR and SIR were compared with the tumour cellularity. All 32 patients with confirmed recurrence showed increased FDG accumulation in the mass (DAR=4.57±1.89) in comparison with low FDG accumulation in five patients with scar (DAR=1.17±0.43). There was a significant correlation (r=0.661, P<0.001) between the DAR and the tumour diameter. There was no correlation between the DAR and SIR, whereas there was a significant correlation (r=0.565, P<0.01) between the DAR corrected using count recovery coefficient (DAR*) and SIR. In the histopathological findings there was a tendency for the DAR* and SIR to correlate with tumour cellularity. It is concluded that the DAR of recurrent rectal cancer should be evaluated taking into consideration the tumour size and cellularity. (orig.)

  18. Development of HM12 cyclotron for PET

    International Nuclear Information System (INIS)

    Morita, Takuzo; Kawama, Tetsuo; Fujii, Kazuo

    2000-01-01

    In Japan, there are at present more than 30 PET (Positron Emission Tomography) facilities. The movements of medical insurance application to the PET diagnosis using [ 18 F] FDG (2-[ 18 F]-fluoro-2-deoxy-glucose) by the Ministry of Health and Welfare are being enhanced by PET related people. Therefore, more clinical centers using PET system are expected to be built in the near future. HM12 cyclotron was developed to meet such market demands for PET, and the prototype machine has been rent to Cyclotron Radio Isotope Center (CYRIC) of Tohoku University since Oct. 1998 for their use of clinical research with positron emitters like 11 C, 13 N, 15 O and 18 F. We got many technical data of HM12 Cyclotron on the clinical base. The data was enough to establish the reliability of HM12 system operation under the clinical condition. The first commercial product of HM12 Cyclotron was delivered to National Cancer Center in March 2000. The final performance test will be finished by the end of June 2000. (author)

  19. Current status and prospects of cardiac PET

    International Nuclear Information System (INIS)

    Yoshida, Katuya

    1999-01-01

    With positron emission tomography (PET), noninvasive measurements of myocardial blood flow and metabolism have now become possible. 1) Myocardial blood flow: We developed a high-resolution PET system for rabbits and showed that myocardial N-13 ammonnia uptake correlated well with flow measure with microspheres. We also demonstrated that a simplified PET protocol using N-13 ammonia or Rb-82 provide noninvasive measurement of coronary flow reserve in dog experiments. This protocol enables to produce estimates of myocardial blood flow in man and that are well correlated with the complex compartment model. 2) Myocardial glucose metabolism: We validated experimentally a simple method to quantify tissue glucose utilization with the brain reference index (BRI) using C-14 deoxyglucose and assessed its clinical feasibility for myocardial PET. 3) Membrane integrity: Loss of cell membrane integrity for trapping the potassium or it's analog is a market of myocardial necrosis/viability. We recently synthetized potassium-38 as a PET tracer and started an experimental study. (author)

  20. Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Myoung Sook Kim

    2010-02-01

    Full Text Available Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH in a significant proportion of primary esophageal squamous cell carcinoma (ESCC samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/beta-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of beta-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/beta-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways.

  1. Nuclear medicine in China

    International Nuclear Information System (INIS)

    Wang, Shihchen; Liu, Xiujie

    1986-01-01

    Since China first applied isotopes to medical research in 1956, over 800 hospitals and research institutions with 4000 staff have taken up nuclear technology. So far, over 120 important biologically active materials have been measured by radioimmunoassay in China, and 44 types of RIA kit have been supplied commercially. More than 50,000 cases of hyperthyroidism have been treated satisfactorily with 131 I. Radionuclide imaging of practically all organs and systems of the human body has been performed, and adrenal imaging and nuclear cardiology have become routine clinical practice in several large hospitals. The thyroid iodine uptake test, renogram tracing and cardiac function studies with a cardiac probe are also commonly used in most Chinese hospitals. The active principles of more than 60 medicinal herbs have been labelled with isotopes in order to study the drug metabolism and mechanism of action. Through the use of labelled neurotransmitters or deoxyglucose, RIA, radioreceptor assay and autoradiography, Chinese researchers have made remarkable achievements in the study of the scientific basis of acupuncture analgesia. In 1980 the Chinese Society of Nuclear Medicine was founded, and since 1981 the Chinese Journal of Nuclear Medicine has been published. Although nuclear medicine in China has already made some progress, when compared with advanced countries, much progress is still to be made. It is hoped that international scientific exchange will be strengthened in the future. (author)

  2. Cancer find and treat the individual: The nuclear medicine approach

    International Nuclear Information System (INIS)

    Britton, K.E.; Granowska, M.

    2002-01-01

    Most cancer surgery and radiotherapy is based on the physical extent of the disease and not the biological extent. Most cancer chemotherapy is based on the clinical trials of the many and may or may not work in the individual. Nuclear Medicine treats the individual in whom it has provided evidence for uptake of the agent for therapy. Radiology requires a mass in tissue, displacing tissue, infiltrating tissue for contrast. Nuclear Medicine does not require a mass. It exploits the subtle differences between the cancer cell and the normal cell for identification. For cancer imaging, Nuclear Medicine has a considerable amplification factor. For the use of F-18 de-oxyglucose (FDG), the glucose transporter protein may be increased 5 - 10 times in the malignant cell and the hexokinase enzyme may be up-regulated 2-5 times. The Positron Emission Tomography (PET) detector may be a hundred fold more sensitive than a conventional gamma camera. For peptides, receptor expression may be increased 500- 10,000 times and antigen expression per cell for monoclonal antibodies between 5000 and 50,000 times. As well as the uptake, the residence time of the radiopharmaceutical is important so that what is taken up stays a sufficient length of time for imaging and/or for therapy. A radioactive pinhead is identifiable if it has enough radioactivity on it and a detector sensitive enough to detect it. For tumours less than 1.5 cm in diameter, size is not the determinant of detection

  3. Statistical analysis of coding for molecular properties in the olfactory bulb

    Directory of Open Access Journals (Sweden)

    Benjamin eAuffarth

    2011-07-01

    Full Text Available The relationship between molecular properties of odorants and neural activities is arguably one of the most important issues in olfaction and the rules governing this relationship are still not clear. In the olfactory bulb (OB, glomeruli relay olfactory information to second-order neurons which in turn project to cortical areas. We investigate relevance of odorant properties, spatial localization of glomerular coding sites, and size of coding zones in a dataset of 2-deoxyglucose images of glomeruli over the entire OB of the rat. We relate molecular properties to activation of glomeruli in the OB using a nonparametric statistical test and a support-vector machine classification study. Our method permits to systematically map the topographic representation of various classes of odorants in the OB. Our results suggest many localized coding sites for particular molecular properties and some molecular properties that could form the basis for a spatial map of olfactory information. We found that alkynes, alkanes, alkenes, and amines affect activation maps very strongly as compared to other properties and that amines, sulfur-containing compounds, and alkynes have small zones and high relevance to activation changes, while aromatics, alkanes, and carboxylics acid recruit very big zones in the dataset. Results suggest a local spatial encoding for molecular properties.

  4. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    International Nuclear Information System (INIS)

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  5. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  6. Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Porrino, L.J.; Domer, F.R.; Crane, A.M.; Sokoloff, L.

    1988-05-01

    The 2-(/sup 14/C)deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.

  7. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    International Nuclear Information System (INIS)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J.

    1987-01-01

    The effects of cold exposure and insulin injection on the rates of net 2-[ 3 H]deoxyglucose uptake (K i ) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K i values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K i increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K i that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake

  8. Differential specificity in the glomerular response profiles for alicyclic, bicyclic and heterocyclic odorants

    Science.gov (United States)

    Johnson, Brett A.; Xu, Zhe; Pancoast, Paige; Kwok, Jennifer; Ong, Joan; Leon, Michael

    2008-01-01

    As part of our ongoing effort to relate stimulus to response in the olfactory system, we tested the hypothesis that the unique chemical structures and odors of various cyclic odorants would be associated with unique spatial response patterns in the glomerular layer of the rat olfactory bulb. To this end, rats were exposed to sets of odorants including monocyclic hydrocarbons, bicyclic compounds, and various heterocyclic structures containing oxygen or nitrogen in the ring. Relative activity across the entire layer was assessed by mapping uptake of 2-deoxyglucose into anatomically standardized data matrices. Whereas monocyclic hydrocarbons evoked patterns similar to those evoked by open-chained hydrocarbon odorants, a set of bicyclic compounds with structures and odors similar to camphor evoked uptake in paired ventral domains not previously associated with any other odorant chemical structures. Despite their unique odors as judged by humans, heterocyclic odorants either evoked uptake in previously characterized areas corresponding to their functional groups or stimulated weak or patchy patterns involving isolated glomeruli. While the patchiness of the patterns may be partly related to the rigidity of the compounds, which would be expected to restrict their interactions to only a few receptors, the weakness of the patterns suggests the possibility of species-specific odorant representations. We conclude that whereas some of the novel cyclic structures indeed were represented by unique patterns in the rat bulb, other unique structures were poorly represented, even when they evoked intense and unique odors in humans. PMID:16958095

  9. Evaluation of steam sterilization conditions for [18F]fludeoxyglucose

    International Nuclear Information System (INIS)

    Santos, Priscilla F.; Nascimento, Leonardo T.; Valente, Eduardo S.; Silva, Juliana B.; Silveira, Marina B.; Ferreira, Soraya Z.

    2011-01-01

    [ 18 F]Flu deoxyglucose ( 18 FDG) is the most commonly used radiopharmaceutical for positron emission tomography. Sterile filtration of the final product into sterile vials using 0.22 μm filter membrane is usually adopted for 18 FDG. However, Good Manufacturing Practice (GMP) guidelines recommend heat sterilization as the method of choice to ensure sterility of pharmaceutical preparations. The aim of this study was to essay different steam sterilization conditions in order to choose the best one for 18 FDG. Three different sterilization conditions were essayed. The first one at 121 deg C for 15 minutes, the second one at 135 deg C for 3.5 minutes and the third one at 133 deg C for 2 minutes. 18 FDG pH-formulation was kept around 6.0. At the end of autoclave cycles, 18 FDG sterility was evaluated by direct inoculation of 18 FDG in culture media and radiochemical purity was determined by TLC and HPLC. Results demonstrated that all essayed conditions were able to ensure 18 FDG sterility, but caused a decrease in radiochemical purity of 18 FDG. Autoclave cycle at 133 deg C for 2 minutes was the best essayed condition for 18 FDG terminal sterilization, once it provided the greater radiochemical purity value and took less time. 18 FDG was able to meet specifications after autoclave cycles, what supports the application of steam sterilization in routine 18 FDG production, in compliance with GMP. (author)

  10. The 18F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

    International Nuclear Information System (INIS)

    Wu Jinchang

    2002-01-01

    In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18 F-Deoxyglucose (FDG) by PET prior to surgery and the DNA content and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46(93.88%) were aneuploidy and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18 F-FDG PET as a non-invasive metabolic imaging technique, may also provide information correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction

  11. Glucose oxidation is critical for CD4+ T cell activation in a mouse model of systemic lupus erythematosus1

    Science.gov (United States)

    Yin, Yiming; Choi, Seung-Chul; Xu, Zhiwei; Zeumer, Leilani; Kanda, Nathalie; Croker, Byron P.; Morel, Laurence

    2015-01-01

    We have previously shown that CD4+ T cells from B6.Sle1.Sle2.Sle3 (TC) lupus mice and patients present a high cellular metabolism, and a treatment combining 2-deoxyglucose (2DG), which inhibits glucose metabolism, and metformin, which inhibits oxygen consumption, normalized lupus T cell functions in vitro and reverted disease in mice. We obtained similar results with B6.lpr mice, another model of lupus, and showed that a continuous treatment is required to maintain the beneficial effect of metabolic inhibitors. Further, we investigated the relative roles of glucose oxidation and pyruvate reduction into lactate in this process.. Treatments of TC mice with either 2DG or metformin were sufficient to prevent autoimmune activation, while their combination was necessary to reverse the process. Treatment of TC mice with dichloroacetate (DCA), an inhibitor of lactate production, failed to effectively prevent or reverse autoimmune pathology. In vitro, CD4+ T cell activation upregulated the expression of genes that favor oxidative phosphorylation. Blocking glucose oxidation inhibited both IFNγ and IL-17 production, which could not be achieved by blocking pyruvate reduction. Overall, our data shows that targeting glucose oxidation is required to prevent or reverse lupus development in mice, which cannot be achieved by simply targeting the pyruvate-lactate conversion. PMID:26608911

  12. Practical no-gold-standard evaluation framework for quantitative imaging methods: application to lesion segmentation in positron emission tomography.

    Science.gov (United States)

    Jha, Abhinav K; Mena, Esther; Caffo, Brian; Ashrafinia, Saeed; Rahmim, Arman; Frey, Eric; Subramaniam, Rathan M

    2017-01-01

    Recently, a class of no-gold-standard (NGS) techniques have been proposed to evaluate quantitative imaging methods using patient data. These techniques provide figures of merit (FoMs) quantifying the precision of the estimated quantitative value without requiring repeated measurements and without requiring a gold standard. However, applying these techniques to patient data presents several practical difficulties including assessing the underlying assumptions, accounting for patient-sampling-related uncertainty, and assessing the reliability of the estimated FoMs. To address these issues, we propose statistical tests that provide confidence in the underlying assumptions and in the reliability of the estimated FoMs. Furthermore, the NGS technique is integrated within a bootstrap-based methodology to account for patient-sampling-related uncertainty. The developed NGS framework was applied to evaluate four methods for segmenting lesions from F-Fluoro-2-deoxyglucose positron emission tomography images of patients with head-and-neck cancer on the task of precisely measuring the metabolic tumor volume. The NGS technique consistently predicted the same segmentation method as the most precise method. The proposed framework provided confidence in these results, even when gold-standard data were not available. The bootstrap-based methodology indicated improved performance of the NGS technique with larger numbers of patient studies, as was expected, and yielded consistent results as long as data from more than 80 lesions were available for the analysis.

  13. Observation of the courses of metastasis using PET

    International Nuclear Information System (INIS)

    Oku, Naoto; Okada, Shoji

    1997-01-01

    Positron Emission Computed Tomography (PET), is a nuclear medical diagnostic method by which tomographic images can be obtained non-invasively at a real time. The positron nuclides; 11 C, 13 N, 15 O or 18 F have comparatively high radioactivities which enable to make functional analysis of very small amounts of the cerebral receptors and cellular metabolism. In addition, PET can be used for the determination of blood flow level and thus, it became possible to study the area involved in learning and memory. Several positron-emitting compounds of low molecular weight have been utilized for medical studies and applications. The early courses of metastasis were investigated using (2- 18 F)2-fluoro-2-deoxyglucose ((2- 18 F)FDG). Metastatic cancerous cells labelled with (2- 18 F)FDG were injected into rodents and the radioactivities were monitored by PET, from an aspect of cell adhesion. B16BL6 and MTLn3 cells accumulated highly in the lung of rats in an early stage and gradually disappeared from the organ, whereas RAW 117 cells specifically accumulated in the liver through the early accumulation in the lung. These results indicate that the degree of early accumulation of malignant cells well reflects the feasibility of metastasis. (M.N.)

  14. Development of a Single Detector Ring Micro Crystal Element Scanner: QuickPET II

    Directory of Open Access Journals (Sweden)

    Robert S. Miyaoka

    2005-04-01

    Full Text Available This article describes a single ring version of the micro crystal element scanner (MiCES and investigation of its spatial resolution imaging characteristics for mouse positron emission tomography (PET imaging. This single ring version of the MiCES system, referred to as QuickPET II, consists of 18 MiCE detector modules mounted as a single ring in a vertical gantry. The system has a 5.76-cm transverse field of view and a 1.98-cm axial field of view. In addition to the scanner and data acquisition system, we have developed an iterative reconstruction that includes a model of the system's detector response function. Evaluation images of line sources and mice have been acquired. Using filtered backprojection, the resolution for a reconstructed line source has been measured at 1.2 mm full width at half maximum. F-18-2-fluoro-2-deoxyglucose mouse PET images are provided. The result shows that QuickPET II has the imaging characteristics to support high-resolution, static mouse PET studies using 18-F labeled compounds.

  15. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

    Science.gov (United States)

    Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

    2017-09-01

    Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

  16. PET/CT in breast carcinoma, combined with sarcoidosis, imitating mediastinal lymph node metastases

    International Nuclear Information System (INIS)

    Garcheva, M.; Hadhyiska, V.; Bochev, P.

    2013-01-01

    PET/CT is a high sensitive, but low-specific method visualizing all the metabolic active processes. Fluoro-deoxyglucose (18F-FDG) uptake is high in tumors, as well as in infections, inflammations, granulomatous processes, post-radiotherapy alterations and in activated organs and tissues like brown fat, adrenals, thyroid, thymus, or bone marrow. This uptake can represent differential diagnostic problem. The clinical case is a young patient with invasive ductal and lobular breast carcinoma, after sectorial resection, without lymph node dissection. The chemotherapy was stopped after 3 courses due to thrombosis of vena cephalica. The local clinical status raises suspicion of recurrence, as the ultrasound. PET/CT was not conclusive about mediastinal lymph node involvement. The histology proves sarcoidosis, which frequently demonstrates symmetric 18F-FDG avid mediastinal and hilar lymph nodes. However the biopsy is mandatory, because of the low specificity of PET/CT for discrimination of this systemic disorder from tumor involvement. Keywords: PET/CT. Differential Diagnostic Problems

  17. Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

    International Nuclear Information System (INIS)

    Li, Ming V.; Chen, Weiqin; Harmancey, Romain N.; Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip; Taegtmeyer, Heinrich; Chan, Lawrence

    2010-01-01

    Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by D-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

  18. Radiopharmaceuticals for the imaging of functional abnormalities of the developing brain

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Kriegel, H.

    1986-01-01

    The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO 2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the brain. The receptor density and the ability of receptors to bind neutrotransmitters is found to be influenced by prenatal irradiation. It is expected that relations between alterations in the developing brain and its postnatal function may be explored in this way. (orig.)

  19. Urinary incontinence and its functional anatomy in frontotemporal lobar degenerations

    International Nuclear Information System (INIS)

    Perneczky, Robert; Diehl-Schmid, Janine; Foerstl, Hans; Kurz, Alexander; Drzezga, Alexander; May, Florian

    2008-01-01

    The frontal lobes play a crucial role in micturition control. However, no reports exist on the functional role of distinct frontal brain regions in urinary incontinence (UIC) in patients with a neurodegenerative damage of the frontal lobe. The aim of the present study was therefore to explore if functional brain lesions were associated with UIC in patients suffering from frontotemporal lobar degenerations (FTLD). Forty-four patients, including eight incontinent subjects, underwent cranial positron emission tomography scanning with 18 F-fluoro-2-deoxy-glucose ( 18 F-FDG PET) to assess the relative metabolic rate of glucose (rCMRglc). Group comparisons of rCMRglc were conducted in SPM2 to identify brain regions where the group of incontinent patients (FTLD+UIC) had significant alterations compared with the group without UIC (FTLD-UIC). At the stringent statistical threshold of p < 0.05, corrected for multiple comparisons according to the family-wise error rate, the statistical analysis revealed two significant right-hemispheric hypometabolic clusters located in the premotor/anterior cingulate cortex and the putamen/claustrum/insula. No hypermetabolic regions were found. The present study is the first to provide evidence for brain functional alterations involved in the occurrence of UIC in FTLD. These results provide an important piece of evidence to the understanding of a particularly distressing autonomic nervous system symptom of dementia. (orig.)

  20. GABA-A stimulation in normal volunteers and during temporal epilepsy measured by 18FDG with positron emission tomography

    International Nuclear Information System (INIS)

    Cinotti, L.; Le Bars, D.; Garcia-Larrea, L.; Peyron, R.; Gregoire, M.C.; Lavenne, F.; Comar, D.; Mauguiere, F.; Krogsgaard-Larsen, P.

    1996-01-01

    The γ-amino butyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and it has been evoked in epilepto-genesis. Using a GABA analog, the THIP, we tried to establish if the gabaergic neurotransmission was modified in the epileptic focus. For this purpose, we measured the effects of this specific GABA agonist on the cerebral glucose consumption (CMRGlu) as measured by 18F-fluoro-deoxyglucose ( 18 FDG) with positron emission tomography (PET). Eight patients presenting temporal epilepsy and three normal volunteers received two 18 FDG PET studies, after placebo and THIP injection, in random order. Clinical symptoms and electroencephalographic data demonstrated a trend towards sleepiness and a diminution of alpha waves after THIP injection. CMRGlu was globally increased with THIP in cortical regions, cerebellum and caudate nuclei. The average increase was 17% in grey matter while it did not reach significancy in white matter. Under the placebo condition, the asymmetry between the focus and the controlateral internal temporal zone was 18% as an average, and reduced significantly to 11% after THIP injection. In the external temporal zones, the asymmetry decreased from 28% to 14%. These results suggest that gabaergic inhibition requires energy in the normal brain tissue and in this with temporal epilepsy. Since the asymmetry of glucose consumption tends to diminish, the inhibitory GABA system appears preserved in temporal epilepsy with an enhanced sensitivity in the focus. (Authors). 6 refs., 4 figs

  1. Endogenous endophthalmitis caused by Cryptococcus neoformans Var. Gattii mimicking choroidal tumor: From positron-emission tomography/computed tomography to histopathology

    Directory of Open Access Journals (Sweden)

    Chun-Ju Lin

    2017-01-01

    Full Text Available A 60-year-old immunocompetent female with pneumonia history about 10 years ago suffered from blurred vision overall survival for 3 weeks. Common cold with headache and unintentional body weight loss was also noted recently. Choroidal detachment simulating choroidal tumor was observed in the temporal quadrant. The 18F-fluoro-2-deoxyglucose (FDG positron-emission tomography/computed tomography (CT scan showed focal, mild to moderate FDG uptake in the left lateral orbit, and an enhanced lesion was seen on the recent CT scan. The suspicious choroidal tumor became larger in a week. Phacoemulsification, vitrectomy, and retinal biopsies were performed. Histochemical study of the retinal specimens established the diagnosis of endogenous cryptococcal endophthalmitis. Vitreous culture yielded Cryptococcus neoformans var. gattii. Systemic and topical voriconazole eliminated the infection. In the literature, endogenous endophthalmitis caused by C. neoformans var. gattii has not been reported in detail. The key to successful management lies in early diagnosis. If clinical improvement could not be achieved after conventional management and imaging studies have failed to yield a definite diagnosis, retinal biopsy can be considered.

  2. [Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS)].

    Science.gov (United States)

    Kleinjung, T; Steffens, T; Langguth, B; Eichhammer, P; Marienhagen, J; Hajak, G; Strutz, J

    2006-06-01

    Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability. In 12 patients with chronic tinnitus, fusion of [18F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation. These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

  3. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Energy Technology Data Exchange (ETDEWEB)

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  4. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

    Science.gov (United States)

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2016-01-01

    Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

  5. Growth and ethanol fermentation ability on hexose and pentose sugars and glucose effect under various conditions in thermotolerant yeast Kluyveromyces marxianus

    Energy Technology Data Exchange (ETDEWEB)

    Rodrussamee, Nadchanok; Hirata, Katsushi; Suprayogi [Yamaguchi Univ., Ube (Japan). Graduate School of Medicine; Lertwattanasakul, Noppon; Kosaka, Tomoyuki [Yamaguchi Univ. (Japan). Faculty of Agriculture; Limtong, Savitree [Kasetsart Univ., Bangkok (Thailand). Faculty of Science; Yamada, Mamoru [Yamaguchi Univ., Ube (Japan). Graduate School of Medicine; Yamaguchi Univ. (Japan). Faculty of Agriculture

    2011-05-15

    Ethanol fermentation ability of the thermotolerant yeast Kluyveromyces marxianus, which is able to utilize various sugars including glucose, mannose, galactose, xylose, and arabinose, was examined under shaking and static conditions at high temperatures. The yeast was found to produce ethanol from all of these sugars except for arabinose under a shaking condition but only from hexose sugars under a static condition. Growth and sugar utilization rate under a static condition were slower than those under a shaking condition, but maximum ethanol yield was slightly higher. Even at 40 C, a level of ethanol production similar to that at 30 C was observed except for galactose under a static condition. Glucose repression on utilization of other sugars was observed, and it was more evident at elevated temperatures. Consistent results were obtained by the addition of 2-deoxyglucose. The glucose effect was further examined at a transcription level, and it was found that KmGAL1 for galactokinase and KmXYL1 for xylose reductase for galactose and xylose/arabinose utilization, respectively, were repressed by glucose at low and high temperatures, but KmHXK2 for hexokinase was not repressed. We discuss the possible mechanism of glucose repression and the potential for utilization of K. marxianus in high-temperature fermentation with mixed sugars containing glucose. (orig.)

  6. Sleep Restriction Impairs Blood–Brain Barrier Function

    Science.gov (United States)

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

    2014-01-01

    The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

  7. Sleep restriction impairs blood-brain barrier function.

    Science.gov (United States)

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

    2014-10-29

    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

  8. Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept.

    Science.gov (United States)

    Bural, Gonca G; Torigian, Drew A; Burke, Anne; Houseni, Mohamed; Alkhawaldeh, Khaled; Cucchiara, Andrew; Basu, Sandip; Alavi, Abass

    2010-06-01

    The aim of this study was to compare hepatic standardized uptake values (SUVs) and hepatic metabolic volumetric products (HMVP) between patients of diffuse hepatic steatosis and control subjects with normal livers. Twenty-seven subjects were included in the study (13 men and 14 women; age range, 34-72 years). All had 18F-2-fluoro-2-D-deoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) scans with an interscan interval of 0-5 months. Twelve of 27 subjects had diffuse hepatic steatosis on MRI. The remaining 15 were selected as age-matched controls based on normal liver parenchyma on MRI. Mean and maximum hepatic SUVs were calculated for both patient groups on FDG-PET images. Hepatic volumes were measured from MRI. HMVP in each subject was subsequently calculated by multiplication of hepatic volume by mean hepatic SUV. HMVPs as well as mean and maximum hepatic SUVs were compared between the two study groups. HMVPs, mean hepatic SUVs, and maximum hepatic SUVs were greater (statistically significant, p < 0.05) in subjects with diffuse hepatic steatosis compared to those in the control group. The increase in HMVP is the result of increased hepatic metabolic activity likely related to the diffuse hepatic steatosis. The active inflammatory process related to the diffuse hepatic steatosis is the probable explanation for the increase in hepatic metabolic activity on FDG-PET study.

  9. Evaluation of steam sterilization conditions for [{sup 18}F]fludeoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Priscilla F.; Nascimento, Leonardo T.; Valente, Eduardo S.; Silva, Juliana B.; Silveira, Marina B.; Ferreira, Soraya Z., E-mail: somafe@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

    2011-07-01

    [{sup 18}F]Flu deoxyglucose ({sup 18}FDG) is the most commonly used radiopharmaceutical for positron emission tomography. Sterile filtration of the final product into sterile vials using 0.22 {mu}m filter membrane is usually adopted for {sup 18}FDG. However, Good Manufacturing Practice (GMP) guidelines recommend heat sterilization as the method of choice to ensure sterility of pharmaceutical preparations. The aim of this study was to essay different steam sterilization conditions in order to choose the best one for {sup 18}FDG. Three different sterilization conditions were essayed. The first one at 121 deg C for 15 minutes, the second one at 135 deg C for 3.5 minutes and the third one at 133 deg C for 2 minutes. {sup 18}FDG pH-formulation was kept around 6.0. At the end of autoclave cycles, {sup 18}FDG sterility was evaluated by direct inoculation of {sup 18}FDG in culture media and radiochemical purity was determined by TLC and HPLC. Results demonstrated that all essayed conditions were able to ensure {sup 18}FDG sterility, but caused a decrease in radiochemical purity of {sup 18}FDG. Autoclave cycle at 133 deg C for 2 minutes was the best essayed condition for {sup 18}FDG terminal sterilization, once it provided the greater radiochemical purity value and took less time. {sup 18}FDG was able to meet specifications after autoclave cycles, what supports the application of steam sterilization in routine {sup 18}FDG production, in compliance with GMP. (author)

  10. Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shichun Du

    2014-01-01

    Full Text Available Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1 was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo.

  11. Strategy of diagnosis and treatment for pediatric solid tumor patients using FDG-PET

    International Nuclear Information System (INIS)

    Hosono, Ako; Watanabe, Atsuko; Tsuji, Naoko; Kawamoto, Hiroshi; Makimoto, Atsushi; Tateishi, Ukihide; Terauthi, Takashi

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was investigated in diagnosis and therapeutic planning of childhood and adolescence malignant solid tumors. Evidence was based on 46 patients (25 males) of ages 5-30 y, involving those with rhabdomyosarcoma (17 cases), Ewing's sarcoma (13), osteosarcoma (5), neuroblastoma (4), Wilms' tumor (2), germinoma (2), and each 1 case of ganglioblastoma, retinoblastoma and hepatoblastoma. In total, they underwent 104 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from January 2005 to February 2006. Evaluations were done with the standard uptake value (SUV, 1 x 1 cm ROI of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt.), by recurrence, by early detection of exacerbation and by follow up of residual tumors, of which typical image findings were herein presented. From the aspects of the present purposes, it was concluded that FDG-PET had advantages of high resolution, short imaging time, quantitative diagnosis (SUV) as well as the tumor detection, and had defects of difficulty of detection of tumors of <1 cm size, of distribution to normal or benign tissues and of difficulty of central nervous system (CNS) imaging. (T.I.)

  12. Evaluation of malignant solid tumor in childhood with FDG-PET

    International Nuclear Information System (INIS)

    Ishida, Amane; Goto, Hiroaki; Kuroki, Fumiko

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was examined in evaluation of diagnosis and therapeutic efficacy of childhood malignant solid tumors. Subjects were 32 patients (16 males) of the median age of 7 y (1 - 27 y), involving those with neuroblastoma (9 cases), hepatoblastoma (4), chronic granulomatous disorder (4) and others (each ≤2). They underwent 75 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from May 2001 to December 2003. Standard uptake value (SUV), 1 x 1 cm region of interest (ROI) of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt., was used for evaluation: SUV>1.5 was defined positive. In neuroblastoma, FDG was found to be highly distributed and kinetics of SUV, to be useful for evaluation of therapeutic efficacy and early metastasis detection. In some cases of hepatoblastoma, the therapeutic effectiveness and recurrence were not satisfactorily evaluative. The distribution of FDG was not satisfactory in Wilms' tumor relative to other tumors. The PET was thought to be useful, despite their small case number examined, for those evaluations of Ewing's tumor, dysgerminoma and Langerhans cell histiocytosis. Thus FDG-PET was found useful for detection, evaluation of therapeutic efficacy and early metastasis detection of pediatric malignant solid tumors. (T.I.)

  13. A novel syndrome of abnormal striatum and congenital cataract: evidence for linkage to chromosomes 11.

    Science.gov (United States)

    Al-Owain, M; Al-Zahrani, J; Al-Bakheet, A; Abudheim, N; Al-Younes, B; Aldhalaan, H; Al-Zaidan, H; Colak, D; Almohaileb, F; Abouzied, M E; Al-Fadhli, F; Meyer, B; Kaya, N

    2013-09-01

    We report a consanguineous family of three girls and one boy affected with a novel syndrome involving the lens and the basal ganglia. The phenotype is strikingly similar between affected siblings with cognitive impairment, attention deficit hyperactivity disorder (ADHD), microcephaly, growth retardation, congenital cataract, and dystonia. The magnetic resonance imaging showed unusual pattern of swelling of the caudate heads and thinning of the putamina with severe degree of hypometabolism on the [18F] deoxyglucose positron emission tomography. Furthermore, the clinical assessment provides the evidence that the neurological phenotype is very slowly progressive. We utilized the 10K single-nucleotide polymorphism (SNP) microarray genotyping for linkage analysis. Genome-wide scan indicated a 45.9-Mb region with a 4.2353 logarithm of the odds score on chromosome 11. Affymetrix genome-wide human SNP array 6.0 assay did not show any gross chromosomal abnormality. Targeted sequencing of two candidate genes within the linkage interval (PAX6 and B3GALTL) as well as mtDNA genome sequencing did not reveal any putative mutations. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  15. Neuronal network disturbance after focal ischemia in rats

    International Nuclear Information System (INIS)

    Kataoka, K.; Hayakawa, T.; Yamada, K.; Mushiroi, T.; Kuroda, R.; Mogami, H.

    1989-01-01

    We studied functional disturbances following left middle cerebral artery occlusion in rats. Neuronal function was evaluated by [14C]2-deoxyglucose autoradiography 1 day after occlusion. We analyzed the mechanisms of change in glucose utilization outside the infarct using Fink-Heimer silver impregnation, axonal transport of wheat germ agglutinin-conjugated-horseradish peroxidase, and succinate dehydrogenase histochemistry. One day after occlusion, glucose utilization was remarkably reduced in the areas surrounding the infarct. There were many silver grains indicating degeneration of the synaptic terminals in the cortical areas surrounding the infarct and the ipsilateral cingulate cortex. Moreover, in the left thalamus where the left middle cerebral artery supplied no blood, glucose utilization significantly decreased compared with sham-operated rats. In the left thalamus, massive silver staining of degenerated synaptic terminals and decreases in succinate dehydrogenase activity were observed 4 and 5 days after occlusion. The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway. Terminal degeneration even affected areas remote from the infarct: there were silver grains in the contralateral hemisphere transcallosally connected to the infarct and in the ipsilateral substantia nigra. Axonal transport study showed disruption of the corticospinal tract by subcortical ischemia; the transcallosal pathways in the cortex surrounding the infarct were preserved. The relation between neural function and the neuronal network in the area surrounding the focal cerebral infarct is discussed with regard to ischemic penumbra and diaschisis

  16. Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-"1"9F-NMR

    International Nuclear Information System (INIS)

    Dickinson, Elizabeth; Arnold, John R. P.; Fisher, Julie

    2017-01-01

    The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using "1"9F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.

  17. Efficient automated synthesis of 2-(5-["1"8F]fluoropentyl)-2-methylmalonic acid (["1"8F]ML-10) on a commercial available ["1"8F]FDG synthesis module

    International Nuclear Information System (INIS)

    Liu, Shaoyu; Nie, Dahong; Jiang, Shende; Tang, Ganghua

    2017-01-01

    ["1"8F]ML-10 (2-(5-["1"8F]fluoro-pentyl)-2-methylmalonic acid) is a small molecule positron emission tomography (PET) probe for apoptosis imaging. Automated synthesis of ["1"8F]ML-10 was developed by using two different purification methods through a direct saponification procedure on a modified commercial ["1"8F]Fluoro-2-Deoxyglucose (["1"8F]FDG) synthesizer. C18 purification method 1: The final ["1"8F]ML-10 solution containing ethanol was obtained with radiochemical yields of 60±5% (n=5) at the end of bombardment (EOB) and radiochemical purity of 98% in 35 min. Al_2O_3 and SCX purification method 2: To avoid possible side effects of a conventional ethanol-containing formulation, an new ethanol-free solution of ["1"8F]ML-10 was also developed, the radiochemical yields was 50±5% (n=5, EOB) within 45 min and the radiochemical purity was 98%. - Highlights: • The production of ["1"8F]ML-10 was optimized by using a straightforward saponification procedure. • Automated synthesis was performed on a commonly FDG synthesis module. • An ethanol-containing ["1"8F]ML-10 formulation was obtained with high radiochemical yield in a shorter time. • An ethanol-free formulation method of ["1"8F]ML-10 was also developed.

  18. Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Nataša Nikolić

    2012-01-01

    Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

  19. Second primary tumor in anti-Ma1/2-positive paraneoplastic limbic encephalitis.

    Science.gov (United States)

    Leyhe, T; Schüle, R; Schwärzler, F; Gasser, T; Haarmeier, T

    2006-05-01

    Memory loss can be a symptom of paraneoplastic limbic encephalitis (PLE) a neuropsychiatric disorder associated mostly with small-cell lung cancer and anti-Hu antibodies or with testicular tumors and anti-Ma2 antibodies. We present the case of a patient with temporal coincidence of beginning cognitive decline and diagnosis of a carcinoma of the prostate in whom we diagnosed anti-Ma1/Ma2-positive PLE. The tumor had been completely resected but memory impairment further deteriorated. As the effective treatment of the cancer is considered as the most efficient treatment of a paraneoplastic neurological syndrome (PNS) a second neoplasia was suspected in the patient. By the aid of whole body positron emission tomography with 18-fluorine fluoro-2-deoxy-glucose (FDG-PET) an adenocarcinoma of the cecum could be detected. Two months after surgery anti-Ma antibodies were negative. We conclude that a second neoplasia should be considered, if effective cancer treatment does not lead to improvement or stabilisation of a PNS. Tumor search should be exhaustive and include PET when conventional imaging fails to show a malignancy.

  20. Anatomical and metabolic small-animal whole-body imaging using ring-shaped confocal photoacoustic computed tomography

    Science.gov (United States)

    Xia, Jun; Chatni, Muhammad; Maslov, Konstantin; Wang, Lihong V.

    2013-03-01

    Due to the wide use of animals for human disease studies, small animal whole-body imaging plays an increasingly important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image coregistration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality. Utilizing the novel design of confocal full-ring light delivery and ultrasound transducer array detection, RC-PACT provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

  1. Role of the water extract from Coccinia indica stem on the stimulation of glucose transport in L8 myotubes

    Directory of Open Access Journals (Sweden)

    Chaweewan Jansakul

    2006-11-01

    Full Text Available Hypoglycemic effect of Coccinia indica used for treatment of diabetes in traditional remedies has known to relate with increased transport of glucose into peripheral tissues. However, the cellular mechanisms for this effect remain unclear. This present study reports that the water extract (WE of C. indica stem exhibited a dose-dependent induction of 2-deoxyglucose (2-DG uptake in rat L8 myotubes. Maximal uptake was observed with approximately 3-fold increase in 2-DG transport in 16 h treatment compared with the control. Effect of WE was stronger than that of 1 mM metformin. The effects of insulin and WE were additive. WE-induced glucose uptake was significantly inhibited by cycloheximide and partially reversed by SB203580. GLUT1 protein was markedly increased in response to WE. Conversely, WE had no effect on GLUT4 protein level. Redistribution of GLUT4 to the plasma membrane was demonstrated. Triterpenoids and carbohydrates were detected in WE. In conclusion, new GLUT1 protein synthesis is necessary for WEstimulated glucose transport while p38-MAPK-dependent activation of transporter intrinsic activity partly contributes to WE action. These results may explain and support the use of C. indica for the prevention and treatment of diabetes.

  2. PET in patients with advanced hypopharynx carcinoma and undergoing systemic chemotherapy

    International Nuclear Information System (INIS)

    Haberkorn, U.A.; Strauss, L.G.; Dimitrakopoulou, A.; Knopp, M.V.; Schadel, A.; Helus, F.; Doll, J.K.; van Kaick, G.

    1989-01-01

    The authors discuss how they have preformed 10 double examinations with positron emission tomography (PET) using F-18 deoxyglucose (FDG) before and after one chemotherapeutic cycle with cisplatin and fluorouracil (5-FU). Sixty minutes after intravenous injection of 12 mCi of FDG, three PET images of the tumor region were acquired. The volume of the tumor and/or involved lymph nodes was calculated from CT cross sections. The standardized FDG uptake was increased in all tumors prior to chemotherapeutic treatment (range, 1.28-2.97 DAR). After chemotherapy, the authors notes a decrease in tumor metabolism and tumor volume in eight patients (range, 1.4-2.32 DAR), while in two patients the FDG uptake was unchanged. A correlation coefficient of r =.78 was found for the change in FDG uptake and tumor growth rate. As results demonstrated, PET offers the possibility to study changes of tumor metabolism during chemotherapy and therefore may be used to optimize therapy regimens

  3. Urinary incontinence and its functional anatomy in frontotemporal lobar degenerations

    Energy Technology Data Exchange (ETDEWEB)

    Perneczky, Robert [Technical University Munich Medical School, Department of Psychiatry and Psychotherapy, Munich (Germany); Technische Universitaet Muenchen, Klinik und Poliklinik fuer Psychiatrie und Psychotherapie, Muenchen (Germany); Diehl-Schmid, Janine; Foerstl, Hans; Kurz, Alexander [Technical University Munich Medical School, Department of Psychiatry and Psychotherapy, Munich (Germany); Drzezga, Alexander [Technical University Munich Medical School, Department of Nuclear Medicine, Munich (Germany); May, Florian [Technical University Munich Medical School, Department of Urology, Munich (Germany)

    2008-03-15

    The frontal lobes play a crucial role in micturition control. However, no reports exist on the functional role of distinct frontal brain regions in urinary incontinence (UIC) in patients with a neurodegenerative damage of the frontal lobe. The aim of the present study was therefore to explore if functional brain lesions were associated with UIC in patients suffering from frontotemporal lobar degenerations (FTLD). Forty-four patients, including eight incontinent subjects, underwent cranial positron emission tomography scanning with {sup 18}F-fluoro-2-deoxy-glucose ({sup 18}F-FDG PET) to assess the relative metabolic rate of glucose (rCMRglc). Group comparisons of rCMRglc were conducted in SPM2 to identify brain regions where the group of incontinent patients (FTLD+UIC) had significant alterations compared with the group without UIC (FTLD-UIC). At the stringent statistical threshold of p < 0.05, corrected for multiple comparisons according to the family-wise error rate, the statistical analysis revealed two significant right-hemispheric hypometabolic clusters located in the premotor/anterior cingulate cortex and the putamen/claustrum/insula. No hypermetabolic regions were found. The present study is the first to provide evidence for brain functional alterations involved in the occurrence of UIC in FTLD. These results provide an important piece of evidence to the understanding of a particularly distressing autonomic nervous system symptom of dementia. (orig.)

  4. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Science.gov (United States)

    Frazer, Lauren C; Darville, Toni; Chandra-Kuntal, Kumar; Andrews, Charles W; Zurenski, Matthew; Mintus, Margaret; AbdelRahman, Yasser M; Belland, Robert J; Ingalls, Robin R; O'Connell, Catherine M

    2012-01-01

    Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  5. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Directory of Open Access Journals (Sweden)

    Lauren C Frazer

    Full Text Available Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL in C. caviae. However, 2-deoxyglucose (2DG treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  6. Nuclear medicine and multimodality imaging of pediatric neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Wolfgang Peter; Pfluger, Thomas [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Coppenrath, Eva [Ludwig-Maximilians-University of Munich, Department of Radiology, Munich (Germany)

    2013-04-15

    Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system and is metastatic or high risk for relapse in nearly 50% of cases. Therefore, exact staging with radiological and nuclear medicine imaging methods is crucial for defining the adequate therapeutic choice. Tumor cells express the norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG imaging has several disadvantages, such as limited spatial resolution, limited sensitivity in small lesions and the need for two or even more acquisition sessions. Most of these limitations can be overcome with positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new tracers, such as fluorodopa or somatostatin receptor agonists, have been tested for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are not sufficient for operative or biopsy planning. In this regard, a combination with morphological imaging is indispensable. This article will discuss strategies for primary and follow-up diagnosis in neuroblastoma using different nuclear medicine and radiological imaging methods as well as multimodality imaging. (orig.)

  7. An investigation of bystander effects in Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    DeVeaux, L.C.; Wells, D.P.; Durtschi, L.S.; Reda, M.; Frujinoiu, C.; Harmon, F.

    2003-01-01

    Full text: 'Bystander' effects have been documented in various mammalian cell types and appear to act by two distinct mechanisms. One response requires a functional gap-junction. A non gap-junction-mediated response has also been observed in human cell lines, indicating release of a signaling factor. No analogous response has been investigated in unicellular organisms. Given that DNA damage signaling pathways are present in simple eukaryotes, we investigated bystander signaling effects using a single-celled organism, the fission yeast Schizosaccharomyces pombe. This organism may provide a much simpler model system than higher eukaryotic cells for studying these effects. We measured survival and mutation rate in an unirradiated culture after exposure to an irradiated culture. These two cultures were mixed immediately after irradiation, and any signaling factor that was produced had direct and continuous access to the unirradiated cells during subsequent cell divisions. The irradiated culture was from a multiply auxotrophic strain, whereas the unirradiated culture was from a prototrophic strain. Surviving colonies of the unirradiated culture were thus easily distinguished from those arising from irradiated cells. Mutation rates were measured as forward mutation to 2-deoxyglucose resistance. We have investigated bystander effects with electron and gamma dose from 6 to 20 MeV electron linacs. We varied electron beam energies, dose rates and temporal distributions of dose. The importance of this research stems from the fundamental evolutionary significance of cell signaling of any kind in unicellular systems, representing a major step toward the evolution of multi-cellular states

  8. The use of microelectrode array (MEA) to study the protective effects of potassium channel openers on metabolically compromised HL-1 cardiomyocytes

    International Nuclear Information System (INIS)

    Law, J K Y; Chan, M; Yeung, C K; Rudd, J A; Hofmann, B; Ingebrandt, S; Offenhäusser, A

    2009-01-01

    The microelectrode array (MEA) was used to evaluate the cardioprotective effects of adenosine triphosphate sensitive potassium (K ATP ) channel activation using potassium channel openers (KCOs) on HL-1 cardiomyocytes subjected to acute chemically induced metabolic inhibition. Beat frequency and extracellular action potential (exAP) amplitude were measured in the presence of metabolic inhibitors (sodium azide (NaN 3 ) or 2-deoxyglucose (2-DG)) or KCOs (pinacidil (PIN, a cyanoguanidine derivative, activates sarcolemmal K ATP channels) or SDZ PCO400 (SDZ, a benzopyran derivative, activates mitochondrial K ATP channels)). The protective effects of these KCOs on metabolically inhibited HL-1 cells were subsequently investigated. Signal shapes indicated that NaN 3 and 2-DG reduced the rate of the sodium (Na + ) influx signal as reflected by a reduction in beat frequency. PIN and SDZ appeared to reduce both rate of depolarization and extent of the Na + influx signals. Pre-treating cardiomyocytes with PIN (0.1 mM), but not SDZ, prevented the reduction of beat frequency associated with NaN 3 - or 2-DG-induced metabolic inhibition. The exAP amplitude was not affected by either KCO. The cardioprotective effect of PIN relative to SDZ may be due to the opening of different K ATP channels. This metabolic inhibition model on the MEA may provide a stable platform for the study of cardiac pathophysiology in the future

  9. Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages

    International Nuclear Information System (INIS)

    Nugent, K.M.; Pesanti, E.L.

    1979-01-01

    The effect of mouse-adapted influenza A/PR/8/34 virus on pulmonary macrophage function was evaluated by using an in vitro system which allowed direct virus interaction with macrophages and then separate analysis of the steps required for bacterial clearance by macrophages. Infection of macrophages with this virus resulted in the appearance of a hemagglutinating activity on the macrophage surface; expression of this activity was inhibited by amantadine, 2-deoxyglucose, and cycloheximide and by pretreatment of the virus inoculum with with ultraviolet light and specific antiserum. After influenza infection, net ingestion of viable Staphylococcus aureus by macrophage monolayers was unaltered and there was no change in the fraction of the monolayer which ingested cocci over a wide range of bacterial inputs. Influenza-infected microphages also inactivated intracellular S. aureus at a rate indistinguishable from controls. Therefore, these in vitro studies do not support the hypothesis that the defect in pulmonary antibacterial mechanisms associated with influenza infections results from a direct effect of virus infection on either the phagocytic or bactericidal activity of resistant pulmonary macarophages

  10. Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

    Science.gov (United States)

    Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

    2017-01-01

    The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

  11. Stress proteins in lymphocytes: Membrane stabilization does not affect the heat shock response

    International Nuclear Information System (INIS)

    Hughes, C.S.; Repasky, E.A.; Subjeck, J.R.

    1987-01-01

    Temperatures which have been used to induce heat shock proteins (hsps) have been at the upper physiologic limit or well above this limit. In addition, little attention has been given to the effects of physiologic heat exposures on hsp induction in lymphocytes. The author examined temperatures between 39 0 C and 41 0 C on protein synthesis in the following lymphoid cell lines and cells: BDK, EL-4, JM, DO.11, and in dispersed lymph nodes and thymic tissues. In these studies, 39.5 0 appears to be the threshold for hsp induction (as distinguished by gel electrophoresis). At this temperature the induction of the major hsps at 70 and 89 kDa are observed. Hsp 89 appears to be the most strongly induced in all cells examined. In JM cells, a human cell line, heat shock also induces hsp 68, the non-constitutive hsp at this size. These temperatures do not depress normal levels of protein synthesis. When stearic acid or cholesterol was added to lymphocyte cultures prior to heating (which stabilize membranes), hsp induction appears to occur in a manner indistinguishable from cells heated in normal media. This suggests that membrane fluidity (as influenced by these agents) does not affect or depress the heat shock response in these cells. Finally, the authors observed that 2-deoxyglucose and other inducers of glucose regulated proteins in fibroblasts also induce the major glucose regulated proteins in lymphocytes

  12. Synthesis of high specific activity [1-3H]-D-glucose

    International Nuclear Information System (INIS)

    Saljoughian, M.; Morimoto, Hiromi; Williams, P.G.; Lee, Hakno

    1991-01-01

    Specifically labeled [1- 3 H]-D-glucose has been used for metabolic and mechanistic studies in erythrocytes. In vitro metabolism of the a and b anomers of the tritiated glucose was readily traced by 3 H NMR spectroscopy. Initial studies used labeled glucose obtained by catalytic exchange labeling (at 4.5-9 Ci/mmole, or 15-30% tritiated at the C-1 position), and this necessitated sample glucose concentrations of 2-4 times physiological. The availability of glucose at maximum specific activity (28.7 Ci/mmole, 100% at the C-1 position) would allow the authors to observe metabolic behavior using 1 mM levels of glucose. Accordingly, they have devised a new route for the synthesis of C-1 tritiated glucose, involving the synthesis of 4,6-O-benzylidene-D-gluconolactone followed by reduction with supertritide. Preliminary work with commercial superdeuteride is complete, and chromatographic and NMR analyses are promising. The analogous tritium reactions are currently underway, and experimental results are presented for all stages of investigation. This strategy should be generally applicable to the labeling of many reducing sugars, with the substrates 2-deoxyglucose and maltotriose being of particular interest to their research

  13. FDG-PET for diagnosing prosthetic joint infection: systematic review and metaanalysis

    International Nuclear Information System (INIS)

    Kwee, Thomas C.; Kwee, Robert M.; Alavi, Abass

    2008-01-01

    The aim of this study was to systematically review and metaanalyze published data on the diagnostic performance of 18 F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in detecting prosthetic hip or knee joint infection. A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Two reviewers independently assessed the methodological quality of each study. A metaanalysis of the reported sensitivity and specificity of each study was performed. Subgroup analyses were performed if results of individual studies were heterogeneous. The inclusion criteria were met by 11 studies; there was a total sample size of 635 prostheses. Overall, the studies had good methodological quality. Pooled sensitivity and specificity of FDG-PET for the detection of prosthetic hip or knee joint infection were 82.1% (95%CI = 68.0-90.8%) and 86.6% (95%CI = 79.7-91.4%), respectively. Heterogeneity among the results of individual studies was present (I 2 = 68.8%). Diagnostic performance was influenced by type of joint prostheses (hip prostheses vs. knee prostheses) and type of reconstruction method used (filtered back vs. iterative) (p = 0.0164 and p = 0.0235, respectively). In this metaanalysis, overall diagnostic performance of FDG-PET was moderate to high. Caution is warranted, however, because results of individual studies were heterogeneous and could not be fully explored. Future studies should further explore potential causes of heterogeneity and validate the use of FDG-PET for diagnosing prosthetic joint infection. (orig.)

  14. Hierarchical multivariate covariance analysis of metabolic connectivity.

    Science.gov (United States)

    Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

    2014-12-01

    Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).

  15. Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

    2010-08-15

    Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

  16. The role of (18)F-FDG positron emission tomography in the follow-up of liver tumors treated with (90)Yttrium radioembolization.

    Science.gov (United States)

    Bagni, Oreste; Filippi, Luca; Schillaci, Orazio

    2015-01-01

    In the last years, radioembolization (RE) has emerged as a novel technique for the treatment of malignant hepatic lesions using (90)Y embedded in spheres, which are infused directly into the hepatic arterial circulation. (90)Y-spheres, once implanted in liver, can release a significant radiation burden to neoplastic cells with a relative low dose to normal parenchyma. (90)Y RE results as a combination of embolization and radiation therapy, thus the standard radiologic follow up modalities may be not sufficiently accurate to assess tumor response to treatment. (18)Fluoro-deoxyglucose Positron Emission Tomography ((18)F-FDG PET) detects glucose uptake and metabolic activity in tumor cells. (18)F-FDG PET has become a well established diagnostic tool in many oncological scenarios. Furthermore, PET response criteria (PERCIST) have been recently introduced to categorize the metabolic response to therapy of cancer patients. Several semiquantitative parameters, such as SUVmax and its changes, the Functional Tumor Volume and the Total Lesion Glycolysis can be useful to accurately assess tumor changes after therapy. The purpose of this article is to present the literature on the role of (18)F-FDG PET in the evaluation of patients with primary and secondary liver tumors treated with (90)Y RE.

  17. Unexpected finding of elevated glucose uptake in fibrous dysplasia mimicking malignancy: contradicting metabolism and morphology in combined PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Stegger, Lars; Weckesser, Matthias [University Hospital of Muenster, Department of Nuclear Medicine (Germany); Juergens, Kai U.; Wormanns, Dag [University Hospital of Muenster, Department of Clinical Radiology (Germany); Kliesch, Sabine [University Hospital of Muenster, Department of Urology (Germany)

    2007-07-15

    Fibrous dysplasia is a common benign disorder of bone in which fibro-osseous tissue replaces bone spongiosa. Lesions have a typical appearance on computed tomography (CT) images and regularly show a markedly increased uptake in bone scintigraphy using {sup 99m}Tc-labelled methylene diphosphonate ({sup 99m}Tc-MDP) as radiotracer. The glucose avidity of these lesions depicted by positron emission tomography (PET) using the radiolabelled glucose derivative {sup 18}F-fluoro-2-deoxy-glucose (FDG) is less well known since FDG-PET does not have a role in the assessment of this disease. However, single cases have been reported in which fibrous dysplasia was present in patients undergoing FDG-PET scanning for oncological reasons, and no significant FDG uptake was observed for lesions identified as fibrous dysplasia. We report on a 24-year-old man with known fibrous dysplasia who underwent combined FDG-PET/CT scanning because of suspected recurrence of testicular cancer. In contrast to prior reports, a markedly elevated uptake of FDG was seen in numerous locations that were identified as fibrous dysplasia by CT. Based on this result, we conclude that fibrous dysplasia may mimick malignancy in FDG-PET and that coregistered CT may help to resolve these equivocal findings. (orig.)

  18. PET CT imaging: the Philippine experience

    International Nuclear Information System (INIS)

    Santiago, Jonas Y.

    2011-01-01

    Currently, the most discussed fusion imaging is PET CT. Fusion technology has tremendous potential in diagnostic imaging to detect numerous conditions such as tumors, Alzheimer's disease, dementia and neural disorders. The fusion of PET with CT helps in the localization of molecular abnormalities, thereby increasing diagnostic accuracy and differentiating benign or artefact lesions from malignant diseases. It uses a radiotracer called fluro deoxyglucose that gives a clear distinction between pathological and physiological uptake. Interest in this technology is increasing and additional clinical validation are likely to induce more health care providers to invest in combined scanners. It is hope that in time, a better appreciation of its advantages over conventional and traditional imaging modalities will be realized. The first PET CT facility in the country was established at the St. Luke's Medical Center in Quezon City in 2008 and has since then provided a state-of-the art imaging modality to its patients here and those from other countries. The paper will present the experiences so far gained from its operation, including the measures and steps currently taken by the facility to ensure optimum workers and patient safety. Plans and programs to further enhance the awareness of the Filipino public on this advanced imaging modality for an improved health care delivery system may also be discussed briefly. (author)

  19. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Garetto, L P; Goodman, M N

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr......Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase...... in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise......, the stimulation of these processes by insulin was enhanced and continued to be so 2 h later when the muscles of the stimulated leg had substantially repleted their glycogen stores. The results suggest that the increases in insulin-mediated glucose utilization and glycogen synthesis in muscle after exercise...

  20. An animal model of tinnitus: a decade of development.

    Science.gov (United States)

    Jastreboff, P J; Sasaki, C T

    1994-01-01

    Although tinnitus affects approximately 9 million people in the United States, a cure remains elusive and the mechanisms of its origin are speculative. The crucial obstacle in tinnitus research has been the lack of an animal model. Over the last decade we have been creating such a model by combining a variety of methodologies, including a behavioral component, to allow for the detection of tinnitus perception. Initially, 2-deoxyglucose had been used to map changes in the metabolic activity after unilateral destruction of the cochlea. It has been found that the initial decrease of the metabolic rate in the auditory nuclei recovered to preoperative values, which could be attributable to the development of tinnitus. The spontaneous activity of single units recorded from the inferior colliculus before and after salicylate administration revealed an increase of discharges, which might reflect the presence of salicylate-induced tinnitus. Recent data have confirmed, and further elaborated this observation, including the discovery of abnormal, epileptic-like, neuronal activity. Finally, the authors have developed a behavioral model of tinnitus, tested it extensively, and used it to measure tinnitus pitch and loudness. The model is presently used for investigating the hypotheses for the mechanisms of tinnitus.

  1. The role of positron emission tomography in the detection of incidental gastrointestinal tract lesions in patients examined for lung cancer

    International Nuclear Information System (INIS)

    Isobe, Kazutoshi; Hata, Yoshinobu; Sakaguchi, Shinji; Takai, Yujiro; Shibuya, Kazutoshi; Takagi, Keigo; Homma, Sakae

    2010-01-01

    The purpose of this study was to clarify the clinical characteristics of lung cancer patients with abnormal accumulation in the gastrointestinal tract by fluoro-2-deoxyglucose positron emission tomography (PET). Of the 968 consecutive patients with primary lung cancer who underwent PET from October 2005 through September 2009, 26 patients had local abnormal accumulation in the gastrointestinal tract. We retrospectively compared the localization of abnormal accumulation in the gastrointestinal tract, standardized uptake value (SUV)max (1 hour), and the final clinical diagnosis. The site of abnormal accumulation was the esophagus in 1 case, the stomach in 8 and the small intestine to large intestine in 17. In 15 out of 26 (57%) cases with true PET positive results, there was esophageal cancer in 1 case, gastric cancer in 2, gastrointestinal stromal tumor in 1, colon cancer in 8, and 1 each of metastasis to the stomach, small intestine and large intestine from lung cancer. In 11 cases with false PET-positive results, there was a stomach polyp in 1 case, gastritis in 3, colon polyp in 1, diverticulitis in 1 and normal physiologic accumulation in 5. There were no differences in mean SUVmax among malignant lesions, benign lesions, and normal physiologic accumulation. We should perform endoscopy of the digestive tract to detect malignant lesions with high incidence rates when PET shows localalized abnormal accumulation in the gastrointestinal, tract in patients with lung cancer. (author)

  2. Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

    International Nuclear Information System (INIS)

    Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

    1983-01-01

    The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([ 123 I]isopropyl-iodoamphetamine[IMP])-glucose utilization ([ 14 C]2-deoxyglucose), and protein synthesis ([ 14 C]leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of [ 123 I]IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in [ 14 C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury

  3. Donepezil- and scopolamine-induced rCMRglu changes assessed by PET in conscious rhesus monkeys

    International Nuclear Information System (INIS)

    Asai, Makoto; Fujikawa, Akihiko; Noda, Akihiro; Miyoshi, Sosuke; Nishimura, Shintaro; Matsuoka, Nobuya

    2009-01-01

    [ 18 F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is a useful tool for measuring the regional cerebral metabolic rate of glucose (rCMRglu), which is an index of neuronal activity. Donepezil, an acetylcholine esterase inhibitor (AChEI), has been recommended as a treatment option for patients with Alzheimer's disease (AD). We aimed to characterize the effects of donepezil on rCMRglu using FDG-PET in non-human primates. We investigated the effects of administration of donepezil (500 μg/kg, intramuscularly (i.m.)), the non-selective muscarinic ACh receptor antagonist scopolamine (30 μg/kg, i.m.), and the coadministration of both drugs on the rCMRglu of conscious young rhesus monkeys. Donepezil increased the rCMRglu in all regions of interest except in the thalamus. Scopolamine treatment also increased the rCMRglu in all regions of interest except the cerebellum and thalamus. However, these effects disappeared with coadministration of the drugs. This PET study showed that administration of donepezil or scopolamine alone increased the rCMRglu in conscious rhesus monkeys. We also found that the donepezil-induced increase was abolished by simultaneous administration of scopolamine, suggesting that muscarinic ACh receptor function plays an important role in the effect of donepezil. (author)

  4. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    International Nuclear Information System (INIS)

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O'Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [ 14 C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor

  5. Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: dynamic responses to depolarization and sensitivity to pioglitazone

    Science.gov (United States)

    Pancani, Tristano; Anderson, Katie L.; Porter, Nada M.; Thibault, Olivier

    2011-01-01

    Neuronal Ca2+ dyshomeostasis associated with cognitive impairment and mediated by changes in several Ca2+ sources has been seen in animal models of both aging and diabetes. In the periphery, dysregulation of intracellular Ca2+ signals may contribute to the development of insulin resistance. In the brain, while it is well-established that type 2 diabetes mellitus is a risk factor for the development of dementia in the elderly, it is not clear whether Ca2+ dysregulation might also affect insulin sensitivity and glucose utilization. Here we present a combination of imaging techniques testing the disappearance of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as an indication of glycolytic activity in neurons and astrocytes. Our work shows that glucose utilization at rest is greater in neurons compared to astrocytes, and ceases upon activation in neurons with little change in astrocytes. Pretreatment of hippocampal cultures with pioglitazone, a drug used in the treatment of type 2 diabetes, significantly reduced glycolytic activity in neurons and enhanced it in astrocytes. This series of experiments, including FURA-2 and NADH imaging, provides results that are consistent with the idea that Ca2+ levels may rapidly alter glycolytic activity, and that downstream events beyond Ca2+ dysregulation with aging, may alter cellular metabolism in the brain. PMID:21978418

  6. Amyloid-β triggers the release of neuronal hexokinase 1 from mitochondria.

    Directory of Open Access Journals (Sweden)

    Leonardo M Saraiva

    2010-12-01

    Full Text Available Brain accumulation of the amyloid-β peptide (Aβ and oxidative stress underlie neuronal dysfunction and memory loss in Alzheimer's disease (AD. Hexokinase (HK, a key glycolytic enzyme, plays important pro-survival roles, reducing mitochondrial reactive oxygen species (ROS generation and preventing apoptosis in neurons and other cell types. Brain isozyme HKI is mainly associated with mitochondria and HK release from mitochondria causes a significant decrease in enzyme activity and triggers oxidative damage. We here investigated the relationship between Aβ-induced oxidative stress and HK activity. We found that Aβ triggered HKI detachment from mitochondria decreasing HKI activity in cortical neurons. Aβ oligomers further impair energy metabolism by decreasing neuronal ATP levels. Aβ-induced HKI cellular redistribution was accompanied by excessive ROS generation and neuronal death. 2-deoxyglucose blocked Aβ-induced oxidative stress and neuronal death. Results suggest that Aβ-induced cellular redistribution and inactivation of neuronal HKI play important roles in oxidative stress and neurodegeneration in AD.

  7. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    International Nuclear Information System (INIS)

    Yamada, Akifumi; Momosaki, Sotaro; Hosoi, Rie; Abe, Kohji; Yamaguchi, Masatoshi; Inoue, Osamu

    2009-01-01

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [ 14 C]2-deoxyglucose ([ 14 C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [ 14 C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [ 14 C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [ 14 C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  8. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  9. The effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J J; McCulloch, J

    1983-02-01

    The effects of the dopaminergic agonist apomorphine (1 mg . kg-1 i.v.) upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals, although the magnitude of the reductions in glucose use displayed considerable regional heterogeneity. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use (by 40-60% from conscious levels) were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine (1 mg . kg-1) effected significant increased in glucose utilization in 15 regions of the CNS (e.g., subthalamic nucleus, ventral thalamic nucleus, rostral neocortex, substantia nigra, pars reticulata), and significant reductions in glucose utilization in two regions of the CNS (lateral habenular nucleus and anterior cingulate cortex).

  10. Insulin stimulates phospholipase D-dependent phosphatidylcholine hydrolysis, Rho translocation, de novo phospholipid synthesis, and diacylglycerol/protein kinase C signaling in L6 myotubes.

    Science.gov (United States)

    Standaert, M L; Bandyopadhyay, G; Zhou, X; Galloway, L; Farese, R V

    1996-07-01

    Previous studies have provided conflicting findings on whether insulin activates certain, potentially important, phospholipid signaling systems in skeletal muscle preparations. In particular, insulin effects on the hydrolysis of phosphatidylcholine (PC) and subsequent activation of protein kinase C (PKC) have not been apparent in some studies. Presently, we examined insulin effects on phospholipid signaling systems, diacylglycerol (DAG) production, and PKC translocation/activation in L6 myotubes. We found that insulin provoked rapid increases in phospholipase D (PLD)-dependent hydrolysis of PC, as evidenced by increases in choline release and phosphatidylethanol production in cells incubated in the presence of ethanol. In association with PC-PLD activation, Rho, a small G protein that is known to activate PC-PLD activation, translocated from the cytosol to the membrane fraction in response to insulin treatment. PC-PLD activation was also accompanied by increases in total DAG production and increases in the translocation of both PKC enzyme activity and DAG-sensitive PKC-alpha, -beta, -delta, and -epsilon from the cytosol to the membrane fraction. A potential role for PKC or a related protein kinase in insulin action was suggested by the finding that RO 31-8220 inhibited both PKC enzyme activity and insulin-stimulated [3H]2-deoxyglucose uptake. Our findings provide the first evidence that insulin stimulates Rho translocation and activates PC-PLD in L6 skeletal muscle cells. Moreover, this signaling system appears to lead to increases in DAG/PKC signaling, which, along with other related signaling factors, may regulate certain metabolic processes, such as glucose transport, in these cells.

  11. Preclinical investigation of tolerance and antitumour activity of new fluorodeoxyglucose-coupled chlorambucil alkylating agents.

    Science.gov (United States)

    Miot-Noirault, Elisabeth; Reux, Bastien; Debiton, Eric; Madelmont, Jean-Claude; Chezal, Jean-Michel; Coudert, Pascal; Weber, Valérie

    2011-06-01

    Our strategy is to increase drug accumulation in target tumour cells using specific "vectors" tailored to neoplastic tissue characteristics, which ideally are not found in healthy tissues. The aim of this work was to use 2-fluoro-2-deoxyglucose (FDG) as a drug carrier, in view of its well-known accumulation by most primary and disseminated human tumours. We had previously selected two FDG-cytotoxic conjugates of chlorambucil (CLB), i.e. compounds 21a and 40a, on the basis of their in vitro profiles. Here we investigated the antitumour profile and tolerance of these compounds in vitro and in vivo in two murine cell lines of solid tumours. In vitro, we found that micromolar concentrations of compounds 21a and 40a inhibited proliferation of B16F0 and CT-26 cell lines. Interestingly, compounds 21a and 40a were found to act at different levels in the cell cycle: S and subG1 accumulation for 21a and G2 accumulation for 40a. In vivo, a single-dose-finding study to select the Maximum Tolerated Dose (MTD) by the intraperitoneal route (IP) showed that the two peracetylated glucoconjugates of CLB were less toxic than CLB itself. When given to tumour-bearing mice (melanoma and colon carcinoma models), according to a "q4d × 3" schedule (i.e., three doses at 4-day intervals) both compounds demonstrated a promising antitumour activity, with Log Cell Kill (LCK) values higher than 1.3 in both B16F0 and CT-26 models. Hence compounds 21a and 40a are good candidates for further works to develop new highly active antineoplastic compounds.

  12. Period3 gene in disorder of consciousness: The role of neuroimaging in understanding the relationship between genotype and sleep. A brief communication.

    Science.gov (United States)

    Bedini, Gloria; Bersano, Anna; D'Incerti, Ludovico; Marotta, Giorgio; Rosazza, Cristina; Rossi Sebastiano, Davide; Franceschetti, Silvana; Sattin, Davide; Leonardi, Matilde; Nigri, Anna; Ferraro, Stefania; Parati, Eugenio Agostino

    2017-10-15

    Several methodologies including neuroimaging and sleep evaluation are being developed to complement the clinical bedside examinations in patients with disorder of consciousness (DOC). Recently, we demonstrated a possible association between Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and functional impairment of DOC patients, speculating a possible role of this gene in sleep regulation. To assess whether the degree of structural and metabolic damage of the main brain areas involved in the sleep generation and homeostasis may influence the different outcome of DOC patients carrying the Per3 5/5 genotype in comparison to Per3 4/4 ones. For the present study, we reviewed 44 DOC patients from the Coma Research Centre of the Fondazione IRCCS Istituto Neurologico "C. Besta" of Milan. All patients underwent to polysomnographic sleep evaluation, cerebral structural magnetic resonance imaging (MRI) and 18 F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) analysis. Our DOC patients presented a moderate anatomical (median score 2) and metabolic damage (median value 2.36 SUVmean) of the sleep areas at both MRI and FDG-PET evaluation. Total sleep time seemed to be higher in 5/5 genotype DOC patients (median value Per3 5/5 , 221min, range 126-323min; median value Per3 4/4 , 167min, range 36-477min; and median value Per3 4/5 , 187min, range 29-422min). However, the MRI scores and FDG-PET values of whole brain, overall sleep areas, hypothalamus, midbrain and thalamus did not differ by genotype distribution. Although limited by the small sample size, our data might support the idea that Per3 genetic predisposition in DOC patients could affect impairment and residual cognitive functions through sleep homeostasis independently from structural and/or metabolic integrity of sleep areas. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. ATP depletion during mitotic arrest induces mitotic slippage and APC/CCdh1-dependent cyclin B1 degradation.

    Science.gov (United States)

    Park, Yun Yeon; Ahn, Ju-Hyun; Cho, Min-Guk; Lee, Jae-Ho

    2018-04-27

    ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN 3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly. Additionally, cells successfully progressed through the cell cycle after mitotic slippage, as indicated by EdU incorporation and time-lapse imaging. Although degradation of cyclin B during normal mitotic progression is primarily regulated by APC/C Cdc20 , we observed an unexpected decrease in Cdc20 prior to degradation of cyclin B during mitotic slippage. This decrease in Cdc20 was followed by a change in the binding partner preference of APC/C from Cdc20 to Cdh1; consequently, APC/C Cdh1 , but not APC/C Cdc20 , facilitated cyclin B degradation following ATP depletion. Pulse-chase analysis revealed that ATP depletion significantly abrogated global translation, including the translation of Cdc20 and Cdh1. Additionally, the half-life of Cdh1 was much longer than that of Cdc20. These data suggest that ATP depletion during mitotic arrest induces mitotic slippage facilitated by APC/C Cdh1 -dependent cyclin B degradation, which follows a decrease in Cdc20 resulting from reduced global translation and the differences in the half-lives of the Cdc20 and Cdh1 proteins.

  14. The amine oxidase inhibitor phenelzine limits lipogenesis in adipocytes without inhibiting insulin action on glucose uptake.

    Science.gov (United States)

    Carpéné, Christian; Grès, Sandra; Rascalou, Simon

    2013-06-01

    The antidepressant phenelzine is a monoamine oxidase inhibitor known to inhibit various other enzymes, among them semicarbazide-sensitive amine oxidase (currently named primary amine oxidase: SSAO/PrAO), absent from neurones but abundant in adipocytes. It has been reported that phenelzine inhibits adipocyte differentiation of cultured preadipocytes. To further explore the involved mechanisms, our aim was to study in vitro the acute effects of phenelzine on de novo lipogenesis in mature fat cells. Therefore, glucose uptake and incorporation into lipid were measured in mouse adipocytes in response to phenelzine, other hydrazine-based SSAO/PrAO-inhibitors, and reference agents. None of the inhibitors was able to impair the sevenfold activation of 2-deoxyglucose uptake induced by insulin. Phenelzine did not hamper the effect of lower doses of insulin. However, insulin-stimulated glucose incorporation into lipids was dose-dependently inhibited by phenelzine and pentamidine, but not by semicarbazide or BTT2052. In contrast, all these SSAO/PrAO inhibitors abolished the transport and lipogenesis stimulation induced by benzylamine. These data indicate that phenelzine does not inhibit glucose transport, the first step of lipogenesis, but inhibits at 100 μM the intracellular triacylglycerol assembly, consistently with its long-term anti-adipogenic effect and such rapid action was not found with all the hydrazine derivatives tested. Therefore, the alterations of body weight control consecutive to the use of this antidepressant drug might be not only related to central effects on food intake/energy expenditure, but could also depend on its direct action in adipocytes. Nonetheless, phenelzine antilipogenic action is not merely dependent on SSAO/PrAO inhibition.

  15. Simultaneous determination of local cerebral glucose utilization and blood flow by carbon-14 double-label autoradiography: method of procedure and validation studies in the rat

    International Nuclear Information System (INIS)

    Ginsberg, M.D.; Smith, D.W.; Wachtel, M.S.; Gonzalez-Carvajal, M.; Busto, R.

    1986-01-01

    Validation studies were undertaken to establish a computer-assisted double-label autoradiographic strategy employing [ 14 C]2-deoxyglucose ([ 14 C]2DG) and [ 14 C]iodoantipyrine ([ 14 C]IAP) to measure local CMRglu (LCMRglu) and CBF (LCBF). An organic solvent was used to extract the majority of IAP between first and second film exposures. In contrast to previously published data, all solvents tested produced partial losses of 2DG from tissue, and all allowed 2-6% of IAP to persist even after 5-day washes. Technical-grade chloroform permitted equal retention of unmetabolized and metabolized 2DG. A linear model was established, which was insensitive to the changes in tissue self-absorption that were shown to occur with chloroform extraction. Propagated error in computing tissue [ 14 C]2DG and [ 14 C]IAP was reduced by maximizing IAP extraction (by longer solvent wash times) and by administering 2.5 times as much IAP as 2DG. Fractional 2DG retention was measured in single-label 2DG sections placed on the films, and fractional IAP retention was evaluated by an optimization procedure. With this strategy, double-label values for LCMRglu and LCBF in anesthetized rats agreed with values obtained in matched single-label series to within 5%. The coefficients of variation for the double- and single-label LCMRglu data were virtually identical, whereas the coefficient of variation for double-label LCBF was 1.8 times that of single-label LCBF. The double-label strategy permitted pixel-by-pixel measurement and video display of the LCMRglu/LCBF ratio; the mean value among structures was 0.472 mumol/ml. With proper attention to methodological detail, this double-label strategy shows great promise for routine laboratory application

  16. Performance of intra-procedural 18-fluorodeoxyglucose PET/CT-guided biopsies for lesions suspected of malignancy but poorly visualized with other modalities

    International Nuclear Information System (INIS)

    Cornelis, F.; Silk, M.; Takaki, H.; Durack, J.C.; Erinjeri, J.P.; Sofocleous, C.T.; Siegelbaum, R.H.; Maybody, M.; Solomon, S.B.; Schoder, H.

    2014-01-01

    We sought to evaluate the safety and the diagnostic success rate of percutaneous biopsies performed under intra-procedural 18 F-deoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) guidance for lesions difficult to see with conventional cross-sectional imaging. From 2011 to 2013, consecutive clinically indicated percutaneous PET/CT-guided biopsies of 106 masses (mean size, 3.3 cm; range, 0.7-15.9 cm; SD, 2.9 cm) in bones (n = 33), liver (n = 26), soft tissues (n = 18), lung (n = 15) and abdomen (n = 14) were reviewed. The biopsy procedures were performed following injection of a mean of 255 MBq (SD, 74) FDG. Mean maximal standardized uptake value (SUV) of lesions was 8.8 (SD, 6.3). A systematic review of the histopathological results and outcomes was performed. Biopsies were positive for malignancy in 76 cases (71.7 %, 76/106) and for benign tissue in 30 cases (28.3 %, 30/106). Immediate results were considered adequate for 100 PET/CT biopsies (94.3 %, 100/106) requiring no further exploration, and for the six others (5.7 %, 6/106) benign diagnoses were confirmed after surgery (n = 4) or follow-up (n = 2). The consequent overall sensitivity and the diagnostic success of biopsy were therefore 100 %. No significant differences in terms of detection of malignancy were observed between the different locations. Lesions > 2 cm or with SUV > 4 were not significantly more likely to be malignant. Complications occurred after four biopsies (3.7 %, 4/106). Intra-procedural PET/CT guidance appears as a safe and effective method and allows high diagnostic success of percutaneous biopsies for metabolically active lesions. (orig.)

  17. Distinct accessory cell requirements define two types of rat T cell hybridomas specific for unique determinants in the encephalitogenic 68-86 region of myelin basic protein

    International Nuclear Information System (INIS)

    Mannie, M.D.; Paterson, P.Y.; Thomas, D.W.; Nairn, R.

    1990-01-01

    Six clonotypically unique T cell hybridomas from Lewis rats were used to study accessory cell activities required for class II MHC restricted T cell responses to the 68-86 encephalitogenic sequence of myelin basic protein (MBP). T cell hybrids which were cultured with GP68-86 68-86 sequence of guinea pig MBP (GPMBP) and naive splenocytes (SPL) were induced to produce IL-2 as measured by the CTLL indicator cell line. The hybrids were categorized into two subsets (designated THYB-1 and THYB-2), because two distinct subset-specific pathways of communication between accessory cells and T cells were involved in GPMBP-induced IL-2 production. These pathways were distinguished by the following six observations. First, when the duration of a pulse of SPL with GPMBP was lengthened from 1 to 4 h, these SPL lost their ability to induce IL-2 production by THYB-2 hybrids yet nevertheless retained full stimulatory activity for THYB-1 hybrids. Second, paraformaldehyde fixation of GPMBP-pulsed SPL abrogated an activity necessary for Ag-induced IL-2 production by THYB-2 hybrids. These fixed SPL were nevertheless able to stimulate THYB-1 hybrids, albeit to a lesser extent than viable unfixed SPL. Third, the addition of either cycloheximide, cytochalasin B, or 2-deoxyglucose to an Ag pulse of SPL with GPMBP dramatically inhibited the subsequent responses of THYB-2 hybrids yet had little or no effect upon the reactivity of THYB-1 hybrids. Fourth, thymocytes lacked necessary activities for GPMBP evoked IL-2 production by THYB-2 hybrids yet strongly promoted THYB-1 hybrid responses. Fifth, exposure of SPL to as little as 500 rad of gamma-irradiation markedly attenuated THYB-2 hybrid response to GPMBP but did not affect THYB-1 responses. Sixth, anti-GPMBP responses by THYB-2 hybrids were observed only in the presence of both radioresistant adherent SPL and a distinct population of radiosensitive nonadherent SPL

  18. Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy.

    Science.gov (United States)

    Natali, Andrea; Gastaldelli, Amalia; Camastra, Stefania; Baldi, Simona; Quagliarini, Fabiana; Minicocci, Ilenia; Bruno, Claudio; Pennisi, Elena; Arca, Marcello

    2013-09-01

    The role of adipose triglyceride lipase (ATGL) in intermediate substrates metabolism has not been fully elucidated in humans. Our objective was to evaluate the consequences of ATGL deficiency on body fat distribution, insulin sensitivity, fatty acids metabolism, and energy substrate utilization. Body composition and organ fat content were measured by bioimpedance and (1)H nuclear magnetic resonance spectroscopy; heart glucose metabolism by [(18)F]deoxyglucose positron emission tomography and insulin sensitivity and β-cell function by oral glucose tolerance and 2-step euglycemic-hyperinsulinemic clamp. Lipolysis ([(2)H5]glycerol turnover) and indirect calorimetry were evaluated at fasting, after oral glucose load, during the clamp, and also during an iv epinephrine infusion. These metabolic investigations were carried out during hospitalization. Three patients affected by neutral lipid storage disease with myopathy (NLSDM) due to homozygosity for loss-of-function mutations in the ATGL gene and 6 sex-, age-, and body mass index-matched controls were studied. As expected, NLSDM patients showed diffuse, although heterogeneous, fat infiltration in skeletal muscles associated with increased visceral fat. Although heart and liver were variably affected, fat content in the pancreas was increased in all patients. Compared with healthy controls, NLSDM patients showed impaired insulin response to glucose possibly related to the severe pancreatic steatosis, preserved whole-body insulin sensitivity, and a shift toward glucose metabolism in the heart. Fasting nonesterified fatty acid concentrations as well as basal lipolytic rates and the antilipolytic effect of insulin were normal in NLSDM patients, whereas the lipolytic effect of norepinephrine was impaired. Finally, no significant abnormality in the respiratory quotient was noted in NLSDM patients. In humans, ATGL has a remarkable effect on cellular lipid droplet handling, and its lack causes both perivisceral, skeletal

  19. Modulation of Higher Order Chromatin Conformation in Mammalian Cell Nuclei Can Be Mediated by Polyamines and Divalent Cations.

    Directory of Open Access Journals (Sweden)

    Ashwat Visvanathan

    Full Text Available The organisation of the large volume of mammalian genomic DNA within cell nuclei requires mechanisms to regulate chromatin compaction involving the reversible formation of higher order structures. The compaction state of chromatin varies between interphase and mitosis and is also subject to rapid and reversible change upon ATP depletion/repletion. In this study we have investigated mechanisms that may be involved in promoting the hyper-condensation of chromatin when ATP levels are depleted by treating cells with sodium azide and 2-deoxyglucose. Chromatin conformation was analysed in both live and permeabilised HeLa cells using FLIM-FRET, high resolution fluorescence microscopy and by electron spectroscopic imaging microscopy. We show that chromatin compaction following ATP depletion is not caused by loss of transcription activity and that it can occur at a similar level in both interphase and mitotic cells. Analysis of both live and permeabilised HeLa cells shows that chromatin conformation within nuclei is strongly influenced by the levels of divalent cations, including calcium and magnesium. While ATP depletion results in an increase in the level of unbound calcium, chromatin condensation still occurs even in the presence of a calcium chelator. Chromatin compaction is shown to be strongly affected by small changes in the levels of polyamines, including spermine and spermidine. The data are consistent with a model in which the increased intracellular pool of polyamines and divalent cations, resulting from depletion of ATP, bind to DNA and contribute to the large scale hyper-compaction of chromatin by a charge neutralisation mechanism.

  20. PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

    Science.gov (United States)

    Gulec, Seza A; Daghighian, Farhad; Essner, Richard

    2016-12-01

    Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18 F-deoxyglucose (FDG)-avid tumors. Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

  1. Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Binns, David S.; Callahan, Jason; Mileshkin, Linda; Pirzkall, Andrea; Yu, Wei; Fine, Bernard M.; Conti, Peter; Scott, Andrew M.; Macfarlane, David; Hicks, Rodney J.

    2011-01-01

    The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in 18 F-deoxyglucose (FDG) or 18 F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy. A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting. Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV ave ), to assess reproducibility, showed only a small difference in physiological uptake (-0.006 ± 0.224 in 118 follow-up FDG scans and 0.09 ± 0.81 in 111 follow-up FLT scans). It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol. (orig.)

  2. Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter.

    Science.gov (United States)

    Gunnink, Leesha K; Busscher, Brianna M; Wodarek, Jeremy A; Rosette, Kylee A; Strohbehn, Lauren E; Looyenga, Brendan D; Louters, Larry L

    2017-06-01

    Caffeine has been shown to be a robust uncompetitive inhibitor of glucose uptake in erythrocytes. It preferentially binds to the nucleotide-binding site on GLUT1 in its tetrameric form and mimics the inhibitory action of ATP. Here we demonstrate that caffeine is also a dose-dependent, uncompetitive inhibitor of 2-deoxyglucose (2DG) uptake in L929 fibroblasts. The inhibitory effect on 2DG uptake in these cells was reversible with a rapid onset and was additive to the competitive inhibitory effects of glucose itself, confirming that caffeine does not interfere with glucose binding. We also report for the first time that caffeine inhibition was additive to inhibition by curcumin, suggesting distinct binding sites for curcumin and caffeine. In contrast, caffeine inhibition was not additive to that of cytochalasin B, consistent with previous data that reported that these two inhibitors have overlapping binding sites. More importantly, we show that the magnitude of maximal caffeine inhibition in L929 cells is much lower than in erythrocytes (35% compared to 90%). Two epithelial cell lines, HCLE and HK2, have both higher concentrations of GLUT1 and increased basal 2DG uptake (3-4 fold) compared to L929 cells, and subsequently display greater maximal inhibition by caffeine (66-70%). Interestingly, activation of 2DG uptake (3-fold) in L929 cells by glucose deprivation shifted the responsiveness of these cells to caffeine inhibition (35%-70%) without a change in total GLUT1 concentration. These data indicate that the inhibition of caffeine is dependent on the activity state of GLUT1, not merely on the concentration. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  3. p53 inactivation decreases dependence on estrogen/ERK signalling for proliferation but promotes EMT and susceptility to 3-bromopyruvate in ERα+ breast cancer MCF-7 cells.

    Science.gov (United States)

    Rieber, Manuel; Strasberg-Rieber, Mary

    2014-03-15

    Most breast cancers express the estrogen receptor alpha (ERα(+)), harbor wt TP53, depend on estrogen/ERK signalling for proliferation, and respond to anti-estrogens. However, concomittant activation of the epidermal growth factor receptor (EGFR)/MEK pathway promotes resistance by decreasing estrogen dependence. Previously, we showed that retroviral transduction of mutant p53 R175H into wt TP53 ERα(+) MCF-7 cells induces epidermal growth factor (EGF)-independent proliferation, activation of the EGF receptor (p-EGFR) and some characteristics of epithelial-mesenchymal transition (EMT). To investigate whether p53 inactivation augments ERα(+) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. Introduction of mutant p53 R175H lowered expression of p53-dependent PUMA and p21WAF1, decreased E-cadherin and cytokeratin 18 associated with EMT, but increased the % of proliferating ERα(+)/Ki67 cells, diminishing estrogen dependence. These cells also exhibited higher proliferation in the presence of MEK-inhibitor UO126, reciprocally correlating with preferential susceptibility to the pyruvate analog 3-bromopyruvate (3-BrPA) without a comparable response to 2-deoxyglucose. p53 siRNA silencing by electroporation in wt TP53 MCF-7 cells also decreased estrogen dependence and response to MEK inhibition, while also conferring susceptibility to 3-BrPA. (a) ERα(+) breast cancer cells dysfunctional for TP53 which proliferate irrespective of low estrogen and chemical MEK inhibition are likely to increase metabolic consumption becoming increasingly susceptible to 3-BrPA; (b) targeting the pyruvate pathway may improve response to endocrine therapy in ERα(+) breast cancer with p53 dysfunction. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase.

    Science.gov (United States)

    Rodrigues-Ferreira, Clara; da Silva, Ana Paula Pereira; Galina, Antonio

    2012-02-01

    The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (ΔΨ(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt-HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system.

  5. NUT midline carcinoma mimicking a germ cell tumor: a case report

    International Nuclear Information System (INIS)

    Harada, Yohei; Koyama, Takafumi; Takeuchi, Kengo; Shoji, Kazufusa; Hoshi, Kazuei; Oyama, Yu

    2016-01-01

    NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor. A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC. Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18 F-FDG PET/CT is useful for staging and assessing responses to therapy

  6. Comparison of Tumor Volumes as Determined by Pathologic Examination and FDG-PET/CT Images of Non-Small-Cell Lung Cancer: A Pilot Study

    International Nuclear Information System (INIS)

    Yu Jinming; Li Xinke; Xing Ligang; Mu Dianbin; Fu Zheng; Sun Xiaorong; Sun Xiangyu; Yang Guoren; Zhang Baijiang; Sun Xindong; Ling, C. Clifton

    2009-01-01

    Purpose: To determine the cut-off standardized uptake value (SUV) on 18 F fluoro-2-deoxy-glucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTV path ) for non-small-cell lung cancer (NSCLC). Methods and Materials: Fifteen patients with NSCLC who underwent FDG-PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7-μm sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTV path determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTV PET , was determined as a function of cut-off SUV. The optimal threshold or optimal absolute SUV was defined as the value at which the GTV PET was the same as the GTV path . Results: The fixation process induced a volumetric reduction to 82% ± 10% (range, 62-100%) of the original. The maximal SUV was 10.1 ± 3.6 (range, 4.2-18.7). The optimal threshold and absolute SUV were 31% ± 11% and 3.0 ± 1.6, respectively. The optimal threshold was inversely correlated with GTV path and tumor diameter (p path or tumor diameter (p > 0.05). Conclusion: This study evaluated the use of GTV path as a criterion for determining the optimal cut-off SUV for NSCLC target volume delineation. Confirmatory studies including more cases are being performed.

  7. Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats.

    Science.gov (United States)

    Rutten, Kris; Van Donkelaar, Eva L; Ferrington, Linda; Blokland, Arjan; Bollen, Eva; Steinbusch, Harry Wm; Kelly, Paul At; Prickaerts, Jos Hhj

    2009-07-01

    Phosphodiesterase (PDE) inhibitors prevent the breakdown of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), and are currently studied as possible targets for cognitive enhancement. Earlier studies indicated beneficial effects of PDE inhibitors in object recognition. In this study we tested the effects of three PDE inhibitors on spatial memory as assessed in a place and object recognition task. Furthermore, as both cAMP and cGMP are known vasodilators, the effects of PDE inhibition on cognitive functions could be explained by enhancement of cerebrovascular function. We examined this possibility by measuring the effects of PDE5 and PDE4 inhibitor treatment on local cerebral blood flow and glucose utilization in rats using [14C]-iodoantipyrine and [14C]-2-deoxyglucose quantitative autoradiography, respectively. In the spatial location task, PDE5 inhibition (cGMP) with vardenafil enhanced only early phase consolidation, PDE4 inhibition (cAMP) with rolipram enhanced only late phase consolidation, and PDE2 inhibition (cAMP and cGMP) with Bay 60-7550 enhanced both consolidation processes. Furthermore, PDE5 inhibition had no cerebrovascular effects in hippocampal or rhinal areas. PDE4 inhibition increased rhinal, but not hippocampal blood flow, whereas it decreased glucose utilization in both areas. In general, PDE5 inhibition decreased the ratio between blood flow and glucose utilization, indicative of general oligaemia; whereas PDE4 inhibition increased this ratio, indicative of general hyperemia. Both oligaemic and hyperemic conditions are detrimental for brain function and do not explain memory enhancement. These results underscore the specific effects of cAMP and cGMP on memory consolidation (object and spatial memory) and provide evidence that the underlying mechanisms of PDE inhibition on cognition are independent of cerebrovascular effects.

  8. Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken.

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2008-06-15

    From experiments using a discriminated bead task in young chicks, we have defined when and where adrenoceptors (ARs) are involved in memory modulation. All three ARs subtypes (alpha(1)-, alpha(2)- and beta-ARs) are found in the chick brain and in regions associated with memory. Glucose and glycogen are important in the role of memory consolidation in the chick since increasing glucose levels improves memory consolidation while inhibiting glucose transporters (GLUTs) or glycogen breakdown inhibits memory consolidation. The selective beta(3)-AR agonist CL316243 enhances memory consolidation by a glucose-dependent mechanism and the administration of the non-metabolized glucose analogue 2-deoxyglucose reduces the ability of CL316243 to enhance memory. Agents that reduce glucose uptake by GLUTs and its incorporation into the glycolytic pathway also reduce the effectiveness of CL316243, but do not alter the dose-response relationship to the beta(2)-AR agonist zinterol. However, beta(2)-ARs do have a role in memory related to glycogen breakdown and inhibition of glycogenolysis reduces the ability of zinterol to enhance memory. Both beta(2)- and beta(3)-ARs are found on astrocytes from chick forebrain, and the actions of beta(3)-ARs on glucose uptake, and beta(2)-ARs on the breakdown of glycogen is consistent with an effect on astrocytic metabolism at the time of memory consolidation 30 min after training. We have shown that both beta(2)- and beta(3)-ARs can increase glucose uptake in chick astrocytes but do so by different mechanisms. This review will focus on the role of ARs on memory consolidation and specifically the role of energy metabolism on AR modulation of memory.

  9. Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

    International Nuclear Information System (INIS)

    Grohmann, Malcolm; Stewart, Claire; Welsh, Gavin; Hunt, Linda; Tavare, Jeremy; Holly, Jeff; Shield, Julian; Sabin, Matt; Crowne, Elizabeth

    2005-01-01

    Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNFα exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNFα (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNFα also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNFα exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation

  10. FDG PET/CT appearance of local osteosarcoma recurrences in pediatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Sharp, Susan E.; Gelfand, Michael J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Shulkin, Barry L.; McCarville, M.B. [St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States)

    2017-12-15

    Osteosarcoma is the most common pediatric malignant bone tumor, frequently surgically managed with limb salvage rather than amputation. Local recurrences are seen in up to 9% of osteosarcoma patients, with CT and MRI imaging often limited by metal artifacts. To describe the [F-18]2-fluoro-2-deoxyglucose (FDG) PET/CT appearance of local osteosarcoma recurrences with correlation to findings on other imaging modalities. A retrospective review of pediatric osteosarcoma patients imaged with FDG PET/CT was performed in patients with pathologically proven local recurrences. FDG PET/CT findings were reviewed and correlated with available comparison imaging studies. Ten local osteosarcoma recurrences in eight pediatric osteosarcoma patients were imaged with FDG PET/CT. All eight patients had a local recurrence after limb salvage; two patients had a second local recurrence after amputation. All local recurrences were seen with FDG PET/CT, demonstrating solid (n=5) or peripheral/nodular (n=5) FDG uptake patterns. Maximum standard uptake values (SUVs) ranged from 3.0 to 15.7. In five recurrences imaged with FDG PET/CT and MRI, MRI was limited or nondiagnostic in three. In four recurrences imaged with FDG PET/CT and bone scan, the bone scan was negative in three. Local osteosarcoma recurrences are well visualized by FDG PET/CT, demonstrating either solid or peripheral/nodular FDG uptake with a wide range of maximum SUVs. FDG PET/CT demonstrates the full extent of local recurrences, while MRI can be limited by artifact from metallic hardware. PET/CT appears to be more sensitive than bone scan in detecting local osteosarcoma recurrences. (orig.)

  11. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

    Science.gov (United States)

    Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

    2016-01-01

    Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

  12. Incidental ovarian 18F-FDG accumulation on PET: correlation with the menstrual cycle

    International Nuclear Information System (INIS)

    Kim, Seok-Ki; Kang, Keon Wook; Roh, Ju Won; Sim, Jung Suk; Lee, Eun Sook; Park, Sang-Yoon

    2005-01-01

    The aim of this study was to determine the nature of incidental ovarian 18 F-fluoro-2-deoxyglucose (FDG) accumulation on positron emission tomography (PET) and the correlation with the menstrual cycle and menopause. We identified 19 incidental FDG accumulations in the ovary (FAOs). FDG PET images were compared with other anatomical imaging methods [magnetic resonance imaging (MRI), computed tomography (CT) or ultrasonography (US)]. Pathological findings, FDG PET scan during the next menstrual cycle and follow-up images (PET, CT and MRI) were reviewed. To establish the relation of FAOs to the menstrual cycle, we reviewed whole-body FDG PET acquired from 207 consecutive women and the pre-examination questionnaires, including data regarding the menstrual cycle. All spherical or discoid FAOs were attributed to normally developing ovarian follicles and corpora lutea on the basis of concurrent MRI, US or the follow-up PET scan. Three of the FAOs were proved pathologically to be either normal ovaries or a haemorrhagic corpus luteum. Fifteen FAOs spontaneously disappeared on the short-term follow-up PET scans. Of 207 women, 61 had active menstrual cycles. FAOs were found in 12 out of 61 premenopausal women (20%), appearing between the 10th and 25th days of the menstrual cycle. No FAOs were found in the women who did not have a menstrual cycle. Physiological ovarian FDG accumulation could be found around the time of ovulation and during the early luteal phase of the menstrual cycle in premenopausal woman. Since FAO is dependent on the menstrual cycle, it can be avoided by scheduling PET just after menstruation. (orig.)

  13. Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Duan, X-Y.; Wang, W.; Li, M.; Li, Y.; Guo, Y-M. [PET-CT Center, The First Affiliated Hospital of Xi' an, Jiaotong University, Xi' an, Shaanxi (China)

    2015-02-03

    {sup 18}F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. {sup 18}F-FDG PET/CT scans were performed and different SUV parameters (SUV{sub max}, SUV{sub avg}, SUV{sub T/L}, and SUV{sub T/A}) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV{sub max}, SUV{sub avg}, and SUV{sub T/L} of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV{sub T/L} was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV{sub max} was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV{sub T/L} appeared to be most useful overall, but SUV{sub max} was the best index for adenocarcinoma tumor differentiation.

  14. Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey.

    Science.gov (United States)

    San-Juan, R; Manuel, O; Hirsch, H H; Fernández-Ruiz, M; López-Medrano, F; Comoli, P; Caillard, S; Grossi, P; Aguado, J M

    2015-06-01

    There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. New perspectives in nuclear imaging

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.

    1981-01-01

    In nuclear medicine, biodistribution is studied by quantitative nuclear imaging; chemistry is translated into radio-pharmacology; physics into instrumentation; and biology into physiology. Nuclear medicine can be thought of as applied physiology and physiological chemistry. The modern nuclear chemist is concerned with molecules, with relating chemical structure to biological distributions, as for iminodiacetate compounds. Using mixed ligand analysis, the hepatobiliary agent, HIDA, developed by Loberg, proved an anionic bis-complex with a charge of minus one. Further studies elsewhere showed that the co-ordination number of technetium was 5 and that an oxo-oxygen was in the apical position. From a series of analogues the amount of the complexes excreted in the bile was found to be directly proportional to the natural log of the molecular weight to charge ratio. The trend is towards the synthesis of labelled compounds whose biodistribution depends on their chemical interaction with structurally specific binding sites, i.e. receptors, enzymes or binding sites of active transport systems. Other examples include amino acids for pancreatic imaging; deoxyglucose for studies of regional brain and heart metabolism; fatty acids for studies of the heart; steroid hormones for breast tumours; and muscarinic compounds for study of the cholinergic system of the heart. Most of these compounds are labelled with 11 C, 18 F or 13 N, available only from cyclotrons, but the extension to the more widely available 123 I and sup(99m)Tc is also proceeding rapidly, stimulated chiefly by the success with the positron-emitting compounds. Advances in nuclear imaging include the development of both positron and single photon emission tomography. Biodistribution studies in man permit measurement of regional as well as global function. Improved perception is being augmented by improved quantification and automation

  16. Characterizing bone marrow involvement in Hodgkin's lymphoma by FDG-PET/CT

    International Nuclear Information System (INIS)

    Weiler-Sagie, Michal; Kagna, Olga; Dann, Eldad J.; Ben-Barak, Ayelet; Israel, Ora

    2014-01-01

    Fluoro-deoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is superior to iliac bone marrow biopsy (iBMB) for detection of bone marrow involvement (BMI) in staging of Hodgkin's lymphoma (HL). The present study aims to characterize the patterns and distribution of BMI in HL as determined by FDG-PET/CT. Reports of FDG-PET/CT studies performed for staging of HL were reviewed. BMI was defined as positive iBMB and/or foci of pathological FDG uptake in the skeleton that behaved in concordance with other sites of lymphoma in studies following chemotherapy. Number of FDG uptake foci, their specific location in the skeleton and the presence of corresponding lesions in the CT component of the study, and stage according to the Ann Arbor staging system, were recorded. The study included 473 patients. iBMB was performed in 336 patients. Nine patients had positive iBMB (9/336, 3 %). Seventy-three patients (73/473, 15 %) had FDG-PET/CT-defined BMI. The BM was the only extranodal site of HL in 52/473 patients (11 %). Forty-five patients had three or more foci of pathological skeletal FDG uptake (45/73, 62 %). Sixty-four patients (64/73, 88 %) had at least one uptake focus in the pelvis or vertebrae. In 60 patients (60/73, 82 %), the number of skeletal FDG uptake foci without corresponding CT lesions was equal to or higher than the number of foci with morphological abnormalities. FDG-PET/CT demonstrated BMI in 15 % of patients with newly diagnosed HL. Diagnosis of BMI in HL by FDG-PET/CT was more sensitive than iBMB with potential upstage in 11 % of patients. The most common pattern of FDG-PET/CT BMI was multifocal (at least three foci) skeletal FDG uptake, with at least one focus in the pelvis or vertebrae and no corresponding CT lesions. (orig.)

  17. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.

    Directory of Open Access Journals (Sweden)

    Lisa Mosconi

    Full Text Available After advanced age, female sex is the major risk factor for Alzheimer's disease (AD. The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15, perimenopause (PERI, n = 14 and postmenopause (MENO, n = 14. All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG-Positron Emission Tomography (PET FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's<0.001. A gradient in biomarker abnormalities was most pronounced in MENO, intermediate in PERI, and lowest in CNT (p<0.001. Biomarkers correlated with immediate and delayed memory scores (Pearson's 0.26≤r≤0.32, p≤0.05. These findings validate earlier preclinical findings and indicate emergence of bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that the optimal window of

  18. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  19. The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.

    Directory of Open Access Journals (Sweden)

    Cathrin Rohleder

    2016-07-01

    Full Text Available Prepulse inhibition (PPI is a neuropsychological process during which a weak sensory stimulus (prepulse attenuates the motor response (startle reaction to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: i startle mediation, ii PPI mediation and iii modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood.We therefore combined [18F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e. associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing.Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.

  20. The role of interim FDG PET-CT after induction chemotherapy as a predictor of concurrent chemoradiotherapy efficacy and prognosis for head and neck cancer

    International Nuclear Information System (INIS)

    Kim, Ka-Rham; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Chung, Ik-Joo; Park, Ki Seong; Kang, Sae-Ryung; Kwon, Seong Young; Chung, Woong-Ki; Bae, Woo Kyun

    2018-01-01

    Induction chemotherapy (ICT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) has the advantages of organ preservation and systemic control in head and neck cancer (HNC). Early prediction of CCRT efficacy may help identify patients who will benefit more from surgery than from CCRT. We investigated the role of interim 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (FDG PET-CT) after ICT to predict the efficacy of CCRT and clinical outcomes. Tumor responses were retrospectively reviewed after CCRT based on the Response Evaluation Criteria in Solid Tumors. FDG PET-CT imaging was performed before and after three cycles of TPF. We examined the associations between the metabolic response (percentage decrease in the maximum standardized uptake value [SUVmax] and total metabolic tumor volume [MTV]) after ICT and complete response (CR) to CCRT, progression-free survival (PFS), and overall survival (OS). We studied 43 HNC patients with a median follow-up of 32.7 months. Lymph node (LN) SUVmax and total MTV decreases from baseline after ICT were greater in patients with a CR to CCRT than in non-CR patients (LN SUVmax, 88.8% vs. 62.5%, respectively; total MTV, 99.7% vs. 89.9%, respectively). Decreases in total MTV ≥ 78% and LN SUVmax ≥73% after ICT predicted CR to CCRT and longer OS and PFS. Using interim FDG PET-CT to measure SUVmax and total MTV after three cycles of ICT may be a useful technique for identifying HNC patients who will benefit from CCRT and predicting survival outcomes. (orig.)

  1. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

    Science.gov (United States)

    Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

    2015-09-15

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. Copyright © 2015 the American Physiological Society.

  2. A novel PTP1B inhibitor extracted from Ganoderma lucidum ameliorates insulin resistance by regulating IRS1-GLUT4 cascades in the insulin signaling pathway.

    Science.gov (United States)

    Yang, Zhou; Wu, Fan; He, Yanming; Zhang, Qiang; Zhang, Yuan; Zhou, Guangrong; Yang, Hongjie; Zhou, Ping

    2018-01-24

    Insulin resistance caused by the overexpression of protein tyrosine phosphatase 1 B (PTP1B) as well as the dephosphorylation of its target is one of the main causes of type 2 diabetes (T2D). A newly discovered proteoglycan, Fudan-Yueyang Ganoderma lucidum (FYGL) extracted from Ganoderma lucidum, was first reported to be capable of competitively inhibiting PTP1B activity in vitro in our previous work. In the present study, we sought to reveal the mechanism of PTP1B inhibition by FYGL at the animal and cellular levels. We found that FYGL can decrease blood glucose, reduce body weight and ameliorate insulin resistance in ob/ob mice. Decrease of PTP1B expression and increase of the phosphorylation of PTP1B targets in the insulin signaling pathway of skeletal muscles were observed. In order to clearly reveal the underlying mechanism of the hypoglycemic effect caused by FYGL, we further investigated the effects of FYGL on the PTP1B-involved insulin signaling pathway in rat myoblast L6 cells. We demonstrated that FYGL had excellent cell permeability by using a confocal laser scanning microscope and a flow cytometer. We found that FYGL had a positive effect on insulin-stimulated glucose uptake by using the 2-deoxyglucose (2-DG) method. FYGL could inhibit PTP1B expression at the mRNA level, phosphorylating insulin receptor substrate-1 (IRS1), as well as activating phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt). Finally, FYGL increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and consequently up-regulated the expression of glucose transporter type 4 (GLUT4), promoting GLUT4 transportation to the plasma membrane in PTP1B-transfected L6 cells. Our study provides theoretical evidence for FYGL to be potentially used in T2D management.

  3. Fucosterol activates the insulin signaling pathway in insulin resistant HepG2 cells via inhibiting PTP1B.

    Science.gov (United States)

    Jung, Hyun Ah; Bhakta, Himanshu Kumar; Min, Byung-Sun; Choi, Jae Sue

    2016-10-01

    Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. This study investigated the modulatory effects of fucosterol on the insulin signaling pathway in insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B (PTP1B). In addition, molecular docking simulation studies were performed to predict binding energies, the specific binding site of fucosterol to PTP1B, and to identify interacting residues using Autodock 4.2 software. Glucose uptake was determined using a fluorescent D-glucose analogue and the glucose tracer 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling pathway was detected by Western blot analysis. We found that fucosterol enhanced insulin-provoked glucose uptake and conjointly decreased PTP1B expression level in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 µM in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest that fucosterol stimulates glucose uptake and improves insulin resistance by downregulating expression of PTP1B and activating the insulin signaling pathway. Thus, fucosterol has potential for development as an anti-diabetic agent.

  4. F-18 FDG PET scan findings in patients with pulmonary involvement in the hypereosinophilic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Hoon; Kim, Tae Hoon; Yun, Mi Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)] (and others)

    2005-08-15

    Hypereosinophilic syndrome (HES) is an infiltrative disease of eosinophils affecting multiple organs including the lung. F-18 2-fluoro-2-deoxyglucose (F-18 FDG) may accumulate at sites of inflammation or infection, making interpretation of whole body PET scan difficult in patients with cancer. This study was to evaluate the PET findings of HES with lung involvement and to find out differential PET features between lung malignancy and HES with lung involvement. F-18 FDG PET and low dose chest CT scan was performed for screening of lung cancer. Eight patients who showed ground-glass attenuation (GGA) and consolidation on chest CT scan with peripheral blood eosinophilia were included in this study. The patients with history of parasite infection, allergy and collagen vascular disease were excluded. CT features and FDG PET findings were meticulously evaluated for the distribution of GGA and consolidation and nodules on CT scan and mean and maximal SUV of abnormalities depicted on F-18 FDG PET scan. In eight patients, follow-up chest CT scan and FDG PET scan were done one or two weeks after initial study. F-18 FDG PET scan identified metabolically active lesions in seven out of eight patients. Maximal SUV was ranged from 2.8 to 10.6 and mean SUV was ranged from 2.2 to 7.2. Remaining one patient had maximal SUV of 1.3. On follow-up FDG PET scan taken on from one to four weeks later showed decreased degree of initially noted FDG uptakes or migration of previously noted abnormal FDG uptakes. Lung involvement in the HES might be identified as abnormal uptake foci on FDG PET scan mimicking lung cancer. Follow-up FDG PET and CT scan for the identification of migration or resolution of abnormalities and decrement of SUV would be of help for the differentiation between lung cancer and HES with lung involvement.

  5. F-18 FDG PET scan findings in patients with pulmonary involvement in the hypereosinophilic syndrome

    International Nuclear Information System (INIS)

    Lee, Jae Hoon; Kim, Tae Hoon; Yun, Mi Jin

    2005-01-01

    Hypereosinophilic syndrome (HES) is an infiltrative disease of eosinophils affecting multiple organs including the lung. F-18 2-fluoro-2-deoxyglucose (F-18 FDG) may accumulate at sites of inflammation or infection, making interpretation of whole body PET scan difficult in patients with cancer. This study was to evaluate the PET findings of HES with lung involvement and to find out differential PET features between lung malignancy and HES with lung involvement. F-18 FDG PET and low dose chest CT scan was performed for screening of lung cancer. Eight patients who showed ground-glass attenuation (GGA) and consolidation on chest CT scan with peripheral blood eosinophilia were included in this study. The patients with history of parasite infection, allergy and collagen vascular disease were excluded. CT features and FDG PET findings were meticulously evaluated for the distribution of GGA and consolidation and nodules on CT scan and mean and maximal SUV of abnormalities depicted on F-18 FDG PET scan. In eight patients, follow-up chest CT scan and FDG PET scan were done one or two weeks after initial study. F-18 FDG PET scan identified metabolically active lesions in seven out of eight patients. Maximal SUV was ranged from 2.8 to 10.6 and mean SUV was ranged from 2.2 to 7.2. Remaining one patient had maximal SUV of 1.3. On follow-up FDG PET scan taken on from one to four weeks later showed decreased degree of initially noted FDG uptakes or migration of previously noted abnormal FDG uptakes. Lung involvement in the HES might be identified as abnormal uptake foci on FDG PET scan mimicking lung cancer. Follow-up FDG PET and CT scan for the identification of migration or resolution of abnormalities and decrement of SUV would be of help for the differentiation between lung cancer and HES with lung involvement

  6. Studies on so-called redistribution phenomenon of cerebral blood flow imaging

    International Nuclear Information System (INIS)

    Oba, Hiroshi

    1989-01-01

    To elucidate the relationship between so-called redistribution phenomenon and metabolism or viability of the brain tissue, a new quantitative triple-radionuclide autoradiography was developed, whereby making it possible to compare both late images and reditribution of IMP with cerebral metabolism in experimentally induced unilateral ischemic brain tissue of rats. Iodine-123 IMP and I-125 IMP were used as tracers for early and late imaging, and H-3 amino acid mixture or H-3 H-2 deoxyglucose as a tracer for protein synthesis or glucose metabolism imaging. There was no significant relationship between redistribution index and protein synthesis or glucose metabolism. Protein synthesis was remarkably decreased in the affected hemisphere regardless of redistribution index values. Although the redistribution indices showed a gentle peak at approximately 34 μ mol/100 g/ min of glucose metabolism, there was no obvious relationship between either late images or redistribution index images and glucose metabolism images. Redistribution indices showed a maximum value at approximately 40 to 50 ml/100 g/min of cerebral blood flow. Reverse redistribution was observed with 160 ml/100 g/min or more of flow. Thin layer chromatographic findings were similar in the affected and non-affected resions, suggesting redistribution of a lipophilic IMP metabolite of p-iodoamphetamine in the affected region. In vitro autoradiography revealed no significant reduction in binding ability of IMP to the affected ischemic cortex. In a computer simulation study for brain activity curve, brain activity at 150 min was found to be almost constant at more than 25 ml/100 g/min of flow. IMP redistribution was unlikely to reflect directly either brain metabolism or function, and both blood flow partition coefficient and blood flow values were independently responsible for cerebral kinetics of IMP. (N.K.)

  7. Pre-radiotherapy FDG PET predicts radiation pneumonitis in lung cancer

    International Nuclear Information System (INIS)

    Castillo, Richard; Guerrero, Thomas; Pham, Ngoc; Ansari, Sobiya; Meshkov, Dmitriy; Castillo, Sarah; Li, Min; Olanrewaju, Adenike; Hobbs, Brian; Castillo, Edward

    2014-01-01

    A retrospective analysis is performed to determine if pre-treatment [ 18 F]-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) image derived parameters can predict radiation pneumonitis (RP) clinical symptoms in lung cancer patients. We retrospectively studied 100 non-small cell lung cancer (NSCLC) patients who underwent FDG PET/CT imaging before initiation of radiotherapy (RT). Pneumonitis symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) from the consensus of 5 clinicians. Using the cumulative distribution of pre-treatment standard uptake values (SUV) within the lungs, the 80th to 95th percentile SUV values (SUV 80 to SUV 95 ) were determined. The effect of pre-RT FDG uptake, dose, patient and treatment characteristics on pulmonary toxicity was studied using multiple logistic regression. The study subjects were treated with 3D conformal RT (n = 23), intensity modulated RT (n = 64), and proton therapy (n = 13). Multiple logistic regression analysis demonstrated that elevated pre-RT lung FDG uptake on staging FDG PET was related to development of RP symptoms after RT. A patient of average age and V 30 with SUV 95 = 1.5 was an estimated 6.9 times more likely to develop grade ≥ 2 radiation pneumonitis when compared to a patient with SUV 95 = 0.5 of the same age and identical V 30 . Receiver operating characteristic curve analysis showed the area under the curve was 0.78 (95% CI = 0.69 – 0.87). The CT imaging and dosimetry parameters were found to be poor predictors of RP symptoms. The pretreatment pulmonary FDG uptake, as quantified by the SUV 95 , predicted symptoms of RP in this study. Elevation in this pre-treatment biomarker identifies a patient group at high risk for post-treatment symptomatic RP

  8. Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Trinkaus, Mateya E.; Rischin, Danny; Blum, Rob

    2013-01-01

    For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ( 18 F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent 18 F-FAZA PET scans and 18 F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment 18 F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P=0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P=0.38). Eight patients with baseline hypoxia had post treatment 18 F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P=0.42). Intra-lesional hypoxia, as detected by 18 F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

  9. Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Binns, David S.; Callahan, Jason; Mileshkin, Linda [The Peter MacCallum Cancer Centre, Melbourne (Australia); Pirzkall, Andrea; Yu, Wei; Fine, Bernard M. [Genentech, Inc., South San Francisco, CA (United States); Conti, Peter [University of Southern California Kenneth Norris Medical Center, Los Angeles, CA (United States); Scott, Andrew M. [The University of Melbourne and The Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Victoria (Australia); Macfarlane, David [Queensland PET Service, Royal Brisbane and Women' s Hospital, Brisbane (Australia); Hicks, Rodney J. [The University of Melbourne and The Peter MacCallum Cancer Centre, Departments of Medicine and Radiology, East Melbourne, VIC (Australia); The Peter MacCallum Cancer Centre, Melbourne (Australia)

    2011-04-15

    The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in {sup 18}F-deoxyglucose (FDG) or {sup 18}F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy. A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting. Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of {+-}5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within {+-}15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV{sub ave}), to assess reproducibility, showed only a small difference in physiological uptake (-0.006 {+-} 0.224 in 118 follow-up FDG scans and 0.09 {+-} 0.81 in 111 follow-up FLT scans). It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol. (orig.)

  10. The cerebral neurobiology of anxiety, anxiety displacement, and anxiety denial.

    Science.gov (United States)

    Gottschalk, L A; Fronczek, J; Abel, L; Buchsbaum, M S; Fallon, J H

    2001-01-01

    Previous studies examining the relationship of anxiety scores, derived from the content analysis of speech of normal individuals, have revealed that the anxiety scores occurring in the dreams associated with rapid eye movement (REM) sleep are significantly correlated with localized cerebral glucose metabolic rates assessed by positron emission tomography (PET) scanning. These significant intercorrelations occur in different cerebral areas when the anxiety scores are obtained from mental experiences reported during non-REM sleep or during wakeful silent mentation. The purpose of the present study was to examine the intercorrelations found between anxiety attributed to the self, anxiety-displacement, and anxiety denial measured from computerized content analysis of 5-min verbal reports of subjective thoughts and feelings obtained from wakeful normal subjects and localized cerebral glucose metabolic rates during PET scanning. The subjects were 10 wakeful young males. Their anxiety scores were derived from computerized content analysis of 5-min reports they gave of their subjective thoughts, feelings and fantasies during a 30-min period following an intravenous injection of F D-deoxyglucose (FDG). The subjects were moved 32--45 min after this injection to obtain a PET scan, which records all of the localized cerebral glucose metabolic rates during the 30 min following the FDG injection. Significant intercorrelations of localized cerebral glucose metabolic rates with the scores of self-anxiety, anxiety displacement, and anxiety-denial were found in dissimilar cerebral locations depending on the type of anxiety involved. The significant correlations occurred in brain regions known to be associated with the functions of emotions, cognition, memory, and vision. Specific combinations of cerebral areas, based on glucose metabolic rates, appear to distinguish and be associated with different verbal expressions of anxiety. Replication of this preliminary research will be

  11. Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

    International Nuclear Information System (INIS)

    Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

    1996-01-01

    Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

  12. Brain tumour imaging with PET: a comparison between [{sup 18}F]fluorodopa and [{sup 11}C]methionine

    Energy Technology Data Exchange (ETDEWEB)

    Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt [Department of Nuclear Medicine, Medical School, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Asenbaum, Susanne [Department of Neurology, Medical School, University of Vienna, Vienna (Austria); Marosi, Christine [Department of Oncology, Medical School, University of Vienna, Vienna (Austria); Henk, Christine; Wunderbaldinger, Patrick [Department of Radiology, Medical School, University of Vienna, Vienna (Austria); Czech, Thomas [Department of Neurosurgery, Medical School, University of Vienna, Vienna (Austria)

    2003-11-01

    Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[{sup 18}F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean{+-}SD), were 2.05{+-}0.91 for MET and 2.04{+-}0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of {sup 18}F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

  13. The consequences of long-term glycogen synthase kinase-3 inhibition on normal and insulin resistant rat hearts.

    Science.gov (United States)

    Flepisi, T B; Lochner, Amanda; Huisamen, Barbara

    2013-10-01

    Glycogen synthase kinase-3 (GSK-3) is a serine-threonine protein kinase, discovered as a regulator of glycogen synthase. GSK-3 may regulate the expression of SERCA-2a potentially affecting myocardial contractility. It is known to phosphorylate and inhibit IRS-1, thus disrupting insulin signalling. This study aimed to determine whether myocardial GSK-3 protein and its substrate proteins are dysregulated in obesity and insulin resistance, and whether chronic GSK-3 inhibition can prevent or reverse this. Weight matched male Wistar rats were rendered obese by hyperphagia using a special diet (DIO) for 16 weeks and compared to chow fed controls. Half of each group was treated with the GSK-3 inhibitor CHIR118637 (30 mg/kg/day) from week 12 to16 of the diet period. Biometric and biochemical parameters were measured and protein expression determined by Western blotting and specific antibodies. Ca(2+)ATPase activity was determined spectrophotometrically. Cardiomyocytes were prepared by collagenase perfusion and insulin stimulated 2-deoxy-glucose uptake determined. DIO rats were significantly heavier than controls, associated with increased intra-peritoneal fat and insulin resistance. GSK-3 inhibition did not affect weight but improved insulin resistance, also on cellular level. It had no effect on GSK-3 expression but elevated its phospho/total ratio and elevated IRS-2 expression. Obesity lowered SERCA-2a expression and activity while GSK-3 inhibition alleviated this. The phospho/total ratio of phospholamban underscored inhibition of SERCA-2a in obesity. In addition, signs of myocardial hypertrophy were observed in treated control rats. GSK-3 inhibition could not reverse all the detrimental effects of obesity but may be harmful in normal rat hearts. It regulates IRS-2, SERCA-2a and phospholamban expression but not IRS-1.

  14. High fat feeding results in a decrease in insulin responsiveness of isolated solei

    International Nuclear Information System (INIS)

    Grundleger, M.L.; Preves, D.M.

    1986-01-01

    The relationship between diet and insulin responsiveness was examined in isolated solei from 6 week old female Sprague-Dawley rats. Weanling rats were fed either a high fat (HF) (67%kcal) or a high carbohydrate diet (HC) (67% kcal) for 21 days. A significant decrease in plasma insulin (I) but not glucose was observed in the HF fed rats. Insulin stimulated (IS) glucose (G) metabolism was examined using a maximal concentration of I (20 mU/m1). G uptake was estimated using 14 C-2 deoxyglucose (2DG). Basal and IS 2DG uptake decreased in HF rats. However, I sensitivity but not responsiveness remained intact in the HF rats. Total G utilization (GU) was estimated by the sum of the rate of formation of: 3 H 2 O from 5- 3 H-glucose [glycolysis- (GL)] and 3 H-glycogen (GLY). IS GU decreased in HF versus HC fed rats. I failed to stimulate GL while GLY remained sensitive. Glucose oxidation (GO) was measured by 14 CO 2 . I failed to stimulated GO. Intracellular metabolite concentrations (IC) were measured in solei from HF and HC fed rats. IS IC-G6P decreased in HF compared to HC fed rats. Basal IC-F6P but not IC-F 1.6 BP increased in HF compared to HC fed rats. I failed to stimulate an increase in IC-F 1,6BP concentrations. Glycolytic activators were determined. HF produced a significant decrease in F2, 6BP concentration when compared to HC rats. Prostaglandins (PG) have been implicated in mediating insulin action. HF produced a significant decrease in basal and insulin stimulated PGE 2 . These data demonstrate that postreceptor - postmembrane alterations are in part responsible for the decreased insulin responsiveness observed after HF feeding

  15. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice.

    Science.gov (United States)

    Huang, S-L; Yu, R-T; Gong, J; Feng, Y; Dai, Y-L; Hu, F; Hu, Y-H; Tao, Y-D; Leng, Y

    2012-05-01

    Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP-activated protein kinase (AMPK), and the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated. 2-Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and ob/ob mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system. Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in ob/ob mice. This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in ob/ob mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes.

  16. Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

    Science.gov (United States)

    Gonzalez, Reyna; Pao, Peng-Wen; Hofman, Florence M.; Chen, Thomas C.; Louie, Stan G.; Pirrung, Michael C.; Schönthal, Axel H.

    2013-01-01

    Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD’s anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD’s strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed. PMID:23755268

  17. Effects of algal-produced neurotoxins on metabolic activity in telencephalon, optic tectum and cerebellum of Atlantic salmon (Salmo salar)

    International Nuclear Information System (INIS)

    Bakke, Marit Jorgensen; Horsberg, Tor Einar

    2007-01-01

    Neurotoxins from algal blooms have been reported to cause mortality in a variety of species, including sea birds, sea mammals and fish. Farmed fish cannot escape harmful algal blooms and their potential toxins, thus they are more vulnerable for exposure than wild stocks. Sublethal doses of the toxins are likely to affect fish behaviour and may impair cognitive abilities. In the present study, changes in the metabolic activity in different parts of the Atlantic salmon (Salmo salar) brain involved in central integration and cognition were investigated after exposure to sublethal doses of three algal-produced neurotoxins; saxitoxin (STX), brevetoxin (BTX) and domoic acid (DA). Fish were randomly selected to four groups for i.p. injection of saline (control) or one of the neurotoxins STX (10 μg STX/kg bw), BTX (68 μg BTX/kg bw) or DA (6 mg DA/kg bw). In addition, 14 C-2-deoxyglucose was i.m. injected to measure brain metabolic activity by autoradiography. The three regions investigated were telencephalon (Tel), optic tectum (OT) and cerebellum (Ce). There were no differences in the metabolic activity after STX and BTX exposure compared to the control in these regions. However, a clear increase was observed after DA exposure. When the subregions with the highest metabolic rate were pseudocoloured in the three brain regions, the three toxins caused distinct differences in the respective patterns of metabolic activation. Fish exposed to STX displayed similar patterns as the control fish, whereas fish exposed to BTX and DA showed highest metabolic activity in subregions different from the control group. All three neurotoxins affected subregions that are believed to be involved in cognitive abilities in fish

  18. Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

    Science.gov (United States)

    Gardener, Samantha L; Sohrabi, Hamid R; Shen, Kai-Kai; Rainey-Smith, Stephanie R; Weinborn, Michael; Bates, Kristyn A; Shah, Tejal; Foster, Jonathan K; Lenzo, Nat; Salvado, Olivier; Laske, Christoph; Laws, Simon M; Taddei, Kevin; Verdile, Giuseppe; Martins, Ralph N

    2016-03-31

    Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific

  19. Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

    2005-04-15

    Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

  20. 99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

    Science.gov (United States)

    Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

    2004-04-01

    An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

  1. Comparison of 18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Furumoto, Shozo; Iwata, Ren; Fukuda, Hiroshi; Kawamura, Kazunori; Ishiwata, Kiichi

    2006-01-01

    The distribution characteristics of 18 F-fluoromethylcholine ( 18 F-choline) in tumor and inflammatory tissue were compared with those of 14 C or 3 H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18 F-choline and 3 H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18 F-choline and 14 C-2DG. Whole body (WB) ARG was performed with 18 F-choline. Tumor uptake of 18 F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18 F-choline. 18 F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18 F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18 F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18 F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18 F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18 F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain. (author)

  2. Regional PET/CT after water gastric inflation for evaluating loco-regional disease of gastric cancer

    International Nuclear Information System (INIS)

    Lee, Soo Jin; Lee, Won Woo; Yoon, Hai-Jeon; Lee, Ho-Young; Lee, Kyoung Ho; Kim, Young Hoon; Park, Do Joong; Kim, Hyung-Ho; So, Young

    2013-01-01

    Objective: We aimed to improve diagnostic accuracy of 18 F-fluoro-2-deoxyglucose (FDG) PET/CT for gastric cancer with water gastric inflation. Materials and methods: 44 gastric cancer patients (M:F = 30:14, age ± std = 62.1 ± 14.5y) were enrolled before surgery. Fifty minutes after injection of FDG (0.14 mCi/kg body weight), whole body PET/CT was performed first and then regional PET/CT over gastric area was obtained 80 min post FDG injection after water gastric inflation. Diagnostic accuracies for loco-regional lesions were compared between whole body and regional PET/CT. Results: 48 primary tumors (23 EGC and 25 AGC) and 348 LN stations (61 metastatic and 287 benign) in 44 patients were investigated. Primary tumor sensitivity of whole body PET/CT (50% = 24/48) was significantly improved by regional PET/CT (75% = 36/48, p < 0.005). Sensitivity of whole body PET/CT (24.6% = 15/61) for LN metastasis was also significantly improved by regional PET/CT (36.1% = 22/61, p < 0.01), whereas specificity of whole body PET/CT (99.3% = 285/287) was not compromised by regional PET/CT (98.3% = 282/287, p > 0.05). Higher primary tumor FDG uptake in regional PET/CT indicated shorter progress-free survival (p = 0.0003). Conclusion: Diagnostic accuracy of whole body PET/CT for loco-regional disease of gastric cancer could be significantly improved by regional PET/CT after water gastric inflation and prognosis could be effectively predicted by primary tumor FDG uptake in regional PET/CT

  3. FDG uptake in cervical lymph nodes in children without head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vali, Reza; Bakari, Alaa A.; Marie, Eman; Kousha, Mahnaz; Shammas, Amer [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON (Canada); Charron, Martin [Brampton Nuclear Services, Toronto, ON (Canada)

    2017-06-15

    Reactive cervical lymphadenopathy is common in children and may demonstrate increased {sup 18}F-fluoro-deoxyglucose ({sup 18}F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). We sought to evaluate the frequency and significance of {sup 18}F-FDG uptake by neck lymph nodes in children with no history of head and neck cancer. The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone {sup 18}F-FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased {sup 18}F-FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results. Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049). {sup 18}F-FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is <3.2. The frequency of malignant cervical lymph nodes is higher in PTLD patients compared with other groups. (orig.)

  4. Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer.

    Science.gov (United States)

    Baek, Sora; Choi, Chang-Min; Ahn, Sei Hyun; Lee, Jong Won; Gong, Gyungyub; Ryu, Jin-Sook; Oh, Seung Jun; Bacher-Stier, Claudia; Fels, Lüder; Koglin, Norman; Hultsch, Christina; Schatz, Christoph A; Dinkelborg, Ludger M; Mittra, Erik S; Gambhir, Sanjiv S; Moon, Dae Hyuk

    2012-10-01

    (4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed. Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. [(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01). [(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer.

  5. Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs.

    Science.gov (United States)

    El-Galaly, Tarec Christoffer; Mylam, Karen Juul; Brown, Peter; Specht, Lena; Christiansen, Ilse; Munksgaard, Lars; Johnsen, Hans Erik; Loft, Annika; Bukh, Anne; Iyer, Victor; Nielsen, Anne Lerberg; Hutchings, Martin

    2012-06-01

    The value of performing post-therapy routine surveillance imaging in patients with Hodgkin lymphoma is controversial. This study evaluates the utility of positron emission tomography/computed tomography using 2-[18F]fluoro-2-deoxyglucose for this purpose and in situations with suspected lymphoma relapse. We conducted a multicenter retrospective study. Patients with newly diagnosed Hodgkin lymphoma achieving at least a partial remission on first-line therapy were eligible if they received positron emission tomography/computed tomography surveillance during follow-up. Two types of imaging surveillance were analyzed: "routine" when patients showed no signs of relapse at referral to positron emission tomography/computed tomography, and "clinically indicated" when recurrence was suspected. A total of 211 routine and 88 clinically indicated positron emission tomography/computed tomography studies were performed in 161 patients. In ten of 22 patients with recurrence of Hodgkin lymphoma, routine imaging surveillance was the primary tool for the diagnosis of the relapse. Extranodal disease, interim positron emission tomography-positive lesions and positron emission tomography activity at response evaluation were all associated with a positron emission tomography/computed tomography-diagnosed preclinical relapse. The true positive rates of routine and clinically indicated imaging were 5% and 13%, respectively (P = 0.02). The overall positive predictive value and negative predictive value of positron emission tomography/computed tomography were 28% and 100%, respectively. The estimated cost per routine imaging diagnosed relapse was US$ 50,778. Negative positron emission tomography/computed tomography reliably rules out a relapse. The high false positive rate is, however, an important limitation and a confirmatory biopsy is mandatory for the diagnosis of a relapse. With no proven survival benefit for patients with a pre-clinically diagnosed relapse, the high costs and low

  6. Three-compartment modeling of C-11 N-Methyl spiperone kinetics in the human brain

    International Nuclear Information System (INIS)

    Brooks, R.A.; Wong, D.F.; Di Chiro, G.; Wayner, R.T.; Douglass, K.H.; Frost, J.J.; Larson, S.M.; Wagner, H.N. Jr.

    1984-01-01

    N-Methyl spiperone, as well as spiperone, has been used to study the dopamine receptor system in the brain. The authors have applied a 3-compartment model consisting of vascular, extravascular unbound, and receptor-bound activity to two normal volunteers and one patient with Parkinson's disease. The model differs from that proposed by another study, in that, as in the Sokoloff model for deoxyglucose, there is no explicit term for blood flow. Furthermore, the authors used a 3-compartment model for the cerebellum as well as the caudate/putamen. Serial scans were obtained by PET for up to 2 hrs after injection of the tracer. Time-activity curves were generated over the caudate, putamen and cerebellum. The results indicate a close fit of the observed data to the 3-compatment model. In the model, K1 represents the rate constant of delivery of the tracer in the tissue from the vascular compartment. K2 is the reverse rate constant. K1 was approximately equal to K2 for the cerebellum. In the basal ganglia, K2 was less than K1 due to nonspecific binding in compartment 2. K3 represents the rate constant of binding of the tracer to the receptor binding sites in the cerebral cortex and basal ganglia and to nonspecific binding sites in the cerebellum which contains essentially no dopamine receptors. K4 represents the rate constant for dissociation of the tracer from the receptors. For N-methyl spiperone K4 is very low in the caudate/putamen. The 3-compartment model seemed to fit the data better than the 2-compartment model for both the caudate/putamen and cerebellar activity

  7. Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

    Science.gov (United States)

    Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

    2017-06-01

    Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Fibroblast growth factor 21 improves insulin sensitivity and synergizes with insulin in human adipose stem cell-derived (hASC adipocytes.

    Directory of Open Access Journals (Sweden)

    Darwin V Lee

    Full Text Available Fibroblast growth factor 21 (FGF21 has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR, insulin receptor substrate-1 (IRS-1, and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway.

  9. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  10. CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle.

    Science.gov (United States)

    Witczak, Carol A; Jessen, Niels; Warro, Daniel M; Toyoda, Taro; Fujii, Nobuharu; Anderson, Mark E; Hirshman, Michael F; Goodyear, Laurie J

    2010-06-01

    Studies using chemical inhibitors have suggested that the Ca(2+)-sensitive serine/threonine kinase Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin- and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity of these inhibitors, the specific role that CaMKII may play in the regulation of glucose uptake is not known. We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction-induced glucose uptake in mouse skeletal muscle. Expression vectors containing green fluorescent protein conjugated to a CaMKII inhibitory (KKALHRQEAVDCL) or control (KKALHAQERVDCL) peptide were transfected into tibialis anterior muscles by in vivo electroporation. After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin- and contraction-induced 2-[(3)H]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity approximately 35% compared with control peptide. Insulin-induced glucose uptake was not changed in muscles expressing the inhibitory peptide. In contrast, expression of the inhibitory peptide significantly decreased contraction-induced muscle glucose uptake (approximately 30%). Contraction-induced decreases in muscle glycogen were not altered by the inhibitory peptide. The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites. These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle. However, CaMKII plays a critical role in the regulation of contraction-induced glucose uptake in mouse skeletal muscle.

  11. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

    International Nuclear Information System (INIS)

    Telang, Sucheta; Gragg, Hana; Clem, Brian F; McMasters, Kelly M; Miller, Donald M; Chesney, Jason; Rasku, Mary Ann; Clem, Amy L; Carter, Karen; Klarer, Alden C; Badger, Wesley R; Milam, Rebecca A; Rai, Shesh N; Pan, Jianmin

    2011-01-01

    We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4 + CD25 HI Foxp3 + regulatory T cells and expanded melanoma-specific CD8 + T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients. In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[ 18 F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging. After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year. These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma. http://www.clinicaltrials.gov/ct2/show/NCT00299689

  12. Rac1 governs exercise‐stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

    Science.gov (United States)

    Nielsen, Ida L.; Kleinert, Maximilian; Møller, Lisbeth L. V.; Ploug, Thorkil; Schjerling, Peter; Bilan, Philip J.; Klip, Amira; Jensen, Thomas E.; Richter, Erik A.

    2016-01-01

    Key point Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood.The GTPase Rac1 can be activated by muscle contraction and has been found to be necessary for insulin‐stimulated glucose uptake, although its role in exercise‐stimulated glucose uptake is unknown.We show that Rac1 regulates the translocation of the glucose transporter GLUT4 to the plasma membrane in skeletal muscle during exercise.We find that Rac1 knockout mice display significantly reduced glucose uptake in skeletal muscle during exercise. Abstract Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signalling mechanisms vital for glucose uptake during exercise are not yet fully understood, although the GTPase Rac1 is a candidate molecule. The present study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise‐induced uptake of radiolabelled 2‐deoxyglucose at 65% of maximum running capacity was blocked in soleus muscle and decreased by 80% and 60% in gastrocnemius and tibialis anterior muscles, respectively, in muscle‐specific inducible Rac1 knockout (mKO) mice compared to wild‐type littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 mKO muscle. Our findings implicate Rac1 as a regulatory element critical for controlling glucose uptake during exercise via regulation of GLUT4 translocation. PMID:27061726

  13. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  14. FDG uptake in cervical lymph nodes in children without head and neck cancer.

    Science.gov (United States)

    Vali, Reza; Bakari, Alaa A; Marie, Eman; Kousha, Mahnaz; Charron, Martin; Shammas, Amer

    2017-06-01

    Reactive cervical lymphadenopathy is common in children and may demonstrate increased 18 F-fluoro-deoxyglucose ( 18 F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). We sought to evaluate the frequency and significance of 18 F-FDG uptake by neck lymph nodes in children with no history of head and neck cancer. The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone 18 F-FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased 18 F-FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results. Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049). 18 F-FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is cervical lymph nodes is higher in PTLD patients compared with other groups.

  15. Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

    Directory of Open Access Journals (Sweden)

    Julie eBoulanger Bertolus

    2014-05-01

    Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

  16. PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

    International Nuclear Information System (INIS)

    Rothschild, Sacha; Studer, Gabriela; Seifert, Burkhardt; Huguenin, Pia; Glanzmann, Christoph; Davis, J Bernard; Lütolf, Urs M; Hany, Thomas F; Ciernik, I Frank

    2007-01-01

    Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6–49 months) for the PET/CT-IMRT group and twenty eight months (range, 1–168 months) for the controls. PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings

  17. Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT

    International Nuclear Information System (INIS)

    Wiesmueller, Marco; Schmidt, Daniela; Beck, Michael; Kuwert, Torsten; Gall, Carl C. von; Quick, Harald H.; Navalpakkam, Bharath; Lell, Michael M.; Uder, Michael; Ritt, Philipp

    2013-01-01

    PET/MR hybrid scanners have recently been introduced, but not yet validated. The aim of this study was to compare the PET components of a PET/CT hybrid system and of a simultaneous whole-body PET/MR hybrid system with regard to reproducibility of lesion detection and quantitation of tracer uptake. A total of 46 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 88 min later a second scan using a hybrid PET/MR system. The radioactive tracers used were 18 F-deoxyglucose (FDG), 18 F-ethylcholine (FEC) and 68 Ga-DOTATATE (Ga-DOTATATE). The PET images from PET/CT (PET CT ) and from PET/MR (PET MR ) were analysed for tracer-positive lesions. Regional tracer uptake in these foci was quantified using volumes of interest, and maximal and average standardized uptake values (SUV max and SUV avg , respectively) were calculated. Of the 46 patients, 43 were eligible for comparison and statistical analysis. All lesions except one identified by PET CT were identified by PET MR (99.2 %). In 38 patients (88.4 %), the same number of foci were identified by PET CT and by PET MR . In four patients, more lesions were identified by PET MR than by PET CT , in one patient PET CT revealed an additional focus compared to PET MR . The mean SUV max and SUV avg of all lesions determined by PET MR were by 21 % and 11 % lower, respectively, than the values determined by PET CT (p CT and PET MR were minor, but statistically significant. Nevertheless, a more detailed study of the quantitative accuracy of PET MR and the factors governing it is needed to ultimately assess its accuracy in measuring tissue tracer concentrations. (orig.)

  18. Multiparametric evaluation by simultaneous PET-MRI examination in patients with histologically proven laryngeal cancer

    International Nuclear Information System (INIS)

    Cavaliere, Carlo; Romeo, Valeria; Aiello, Marco; Mesolella, Massimo; Iorio, Brigida; Barbuto, Luigi; Cantone, Elena; Nicolai, Emanuele; Covello, Mario

    2017-01-01

    Highlights: • PET/MRI is feasible and useful for primary staging of laryngeal cancer. • PET/MRI simultaneously provides morphological, metabolic and functional parameters of tumoral laryngeal lesions. • PET/MRI allows an appropriate tumoral staging in terms of lesion extension with significant impact on therapeutic strategies. - Abstract: Objectives: To evaluate the relationship between metabolic 18Fluoro-Deoxyglucose-Positron Emission Tomography (18FDG/PET) and morpho-functional parameters derived by Magnetic Resonance Imaging (MRI) in patients with histologically proven laryngeal cancer. To assess the clinical impact of PET/MRI examination on patient’s staging and treatment planning. Methods: 16 patients with histologically proven laryngeal cancer were enrolled and underwent whole body PET/CT followed by a dedicated PET/MRI of the head/neck region. Data were separately evaluated by two blinded groups: metabolic (SUV and MTV), diffusion (ADC) and perfusion (K trans , V e , k ep and iAUC) maps were obtained by positioning regions of interest (ROIs). Tumoral local extension assessed on PET/MRI was compared to endoscopic findings. Results: A good inter-observer agreement was found in anatomical location and local extension of PET/MRI lesions (Cohen’s kappa 0.9). PET/CT SUV measures highly correlate with ones derived by PET/MRI (e.g., p = 0.96 for measures on VOI). Significant correlations among metabolic, diffusion and perfusion parameters have been detected. PET/MRI had a relevant clinical impact, confirming endoscopic findings (6 cases), helping treatment planning (9 cases), and modifying endoscopic primary staging (1 case). Conclusions: PET/MRI is useful for primary staging of laryngeal cancer, allowing simultaneous collection of metabolic and functional data and conditioning the therapeutic strategies.

  19. Sexual arousal, is it for mammals only?

    Science.gov (United States)

    Ball, Gregory F; Balthazart, Jacques

    2011-05-01

    Sexual arousal has many dimensions and has consequently been defined in various ways. In humans, sexual arousal can be assessed based in part on verbal communication. In male non-human mammalian species, it has been argued that arousal can only be definitively inferred if the subject exhibits a penile erection in a sexual context. In non-mammalian species that lack an intromittent organ, as is the case for most avian species, the question of how to assess sexual arousal has not been thoroughly addressed. Based on studies performed in male Japanese quail, we argue that several behavioral or physiological characteristics provide suitable measures of sexual arousal in birds and probably also in other tetrapods. These indices include, the performance of appetitive sexual behavior in anticipation of copulation (although anticipation and arousal are not synonymous), the activation of specific brain area as identified by the detection of the expression of immediate early genes (fos, egr-1) or by 2-deoxyglucose quantitative autoradiography, and above all, by the release of dopamine in the medial preoptic area as measured by in vivo dialysis. Based on these criteria, it is possible to assess in birds sexual arousal in its broadest sense but meeting the more restrictive definition of arousal proposed for male mammals (erection in an explicit sexual context) is and will probably remain impossible in birds until refinement of in vivo imaging techniques such fMRI allow us to match in different species, with and without an intromittent organ, the brain areas that are activated in the presence of specific stimuli. Copyright © 2010. Published by Elsevier Inc.

  20. Perturbation of human coronary artery endothelial cell redox state and NADPH generation by methylglyoxal.

    Directory of Open Access Journals (Sweden)

    Philip E Morgan

    Full Text Available Diabetes is associated with elevated plasma glucose, increased reactive aldehyde formation, oxidative damage, and glycation/glycoxidation of biomolecules. Cellular detoxification of, or protection against, such modifications commonly requires NADPH-dependent reducing equivalents (e.g. GSH. We hypothesised that reactive aldehydes may modulate cellular redox status via the inhibition of NADPH-generating enzymes, resulting in decreased thiol and NADPH levels. Primary human coronary artery endothelial cells (HCAEC were incubated with high glucose (25 mM, 24 h, 37°C, or methylglyoxal (MGO, glyoxal, or glycolaldehyde (100-500 µM, 1 h, 37°C, before quantification of intracellular thiols and NADPH-generating enzyme activities. Exposure to MGO, but not the other species examined, significantly (P<0.05 decreased total thiols (∼35%, further experiments with MGO showed significant losses of GSH (∼40% and NADPH (∼10%; these changes did not result in an immediate loss of cell viability. Significantly decreased (∼10% NADPH-producing enzyme activity was observed for HCAEC when glucose-6-phosphate or 2-deoxyglucose-6-phosphate were used as substrates. Cell lysate experiments showed significant MGO-dose dependent inhibition of glucose-6-phosphate-dependent enzymes and isocitrate dehydrogenase, but not malic enzyme. Analysis of intact cell or lysate proteins showed that arginine-derived hydroimidazolones were the predominant advanced glycation end-product (AGE formed; lower levels of N(ε-(carboxyethyllysine (CEL and N(ε-(carboxymethyllysine (CML were also detected. These data support a novel mechanism by which MGO exposure results in changes in redox status in human coronary artery endothelial cells, via inhibition of NADPH-generating enzymes, with resultant changes in reduced protein thiol and GSH levels. These changes may contribute to the endothelial cell dysfunction observed in diabetes-associated atherosclerosis.

  1. Advanced modeling in positron emission tomography using Monte Carlo simulations for improving reconstruction and quantification

    International Nuclear Information System (INIS)

    Stute, Simon

    2010-01-01

    Positron Emission Tomography (PET) is a medical imaging technique that plays a major role in oncology, especially using "1"8F-Fluoro-Deoxyglucose. However, PET images suffer from a modest spatial resolution and from high noise. As a result, there is still no consensus on how tumor metabolically active volume and tumor uptake should be characterized. In the meantime, research groups keep producing new methods for such characterizations that need to be assessed. A Monte Carlo simulation based method has been developed to produce simulated PET images of patients suffering from cancer, indistinguishable from clinical images, and for which all parameters are known. The method uses high resolution PET images from patient acquisitions, from which the physiological heterogeneous activity distribution can be modeled. It was shown that the performance of quantification methods on such highly realistic simulated images are significantly lower and more variable than using simple phantom studies. Fourteen different quantification methods were also compared in realistic conditions using a group of such simulated patients. In addition, the proposed method was extended to simulate serial PET scans in the context of patient monitoring, including a modeling of the tumor changes, as well as the variability over time of non-tumoral physiological activity distribution. Monte Carlo simulations were also used to study the detection probability inside the crystals of the tomograph. A model of the crystal response was derived and included in the system matrix involved in tomographic reconstruction. The resulting reconstruction method was compared with other sophisticated methods for modeling the detector response in the image space, proposed in the literature. We demonstrated the superiority of the proposed method over equivalent approaches on simulated data, and illustrated its robustness on clinical data. For a same noise level, it is possible to reconstruct PET images offering a

  2. Factors influencing intracellular uptake and radiosensitization by 2-nitroimidazoles in vitro

    International Nuclear Information System (INIS)

    Brown, D.M.; Gonzalez-Mendez, R.; Brown, J.M.

    1983-01-01

    In this study it is shown that the radiosensitization of hypoxic Chinese hamster ovary (HA-1) cells in vitro by misonidazole (MIS) and other 1-substituted 2-nitroimidazoles depends on the rate and extent of intracellular uptake of these radiosensitizers, which in turn is governed by their lipophilicity [expressed as the octanol:water partition coefficient (P)]. As the lipophilicity of the compounds decreased, the rate of drug entry into the cells was slower, and below P values of approximately 0.05, peak intracellular drug concentrations were found to be lower than that of MIS (P=0.43). In addition, the number of hydroxyl groups on the side chain of the nitroimidazole molecule influenced the uptake of drug into the cells. For compounds of similar P, but differing in the number of side-chain hydroxyl groups, the addition of a single hydroxyl group to the molecule decreased the amount of drug entering the cell by a factor of approximately 2. These compounds enter the cell by nonmediated passive diffusion since altering the energy (ATP) capacity of the cell by 2-deoxyglucose did not affect uptake. It is also shown that increases in temperature or decreases in pH can increase the intracellular uptake of MIS. For example, equal intracellular and extracellular concentrations (100% uptake) of MIS were obtained if cells were heated to 44-45 0 C for 15 min compared to 20-40% uptake at 37 0 C. Increases in MIS uptake by factors of 2 to 3 could be demonstrated within 30 min when cells were incubated in Hanks' balanced salt solution at pH between 6.0 and 6.3 without loss of cell viability. In addition, MIS uptake in aerobic cultured cells varied from 15 to 60% depending on the cell line and culure conditions used

  3. Regulation of palmitoyl-CoA chain elongation by clofibric acid in the liver of Zucker fa/fa rats.

    Science.gov (United States)

    Toyama, Tomoaki; Kudo, Naomi; Mitsumoto, Atsushi; Kawashima, Yoichi

    2005-05-01

    The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats were due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2 (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was significantly increased by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity, SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when Zucker fa/fa rats are given clofibric acid.

  4. Midline oligodendrogliomas as studied by means of computed tomographic, angiographic, and positron-emission tomographic evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Kenji; Kowada, Masayoshi; Sakamoto, Tetsuya; Mineura, Katsuyoshi (Akita Univ. (Japan). Hospital)

    1989-08-01

    Five patients with intraventricular oligodendroglioma involving the lateral ventricle were reviewed by computed tomography (CT), cerebral angiography, and positron-emission tomography (PET) to delineate specific neuroradiological features of the tumors in comparison to those involving the cerebral hemispheres. Intraventricular mass lesions, extending largely from the anterior horn to the body or trigone of the lateral ventricle, were seen as hyperdense tumors in on CT; none was iso- or hypodense. Asymmetrical dilation of the lateral ventricles was noted. Noteworthy was the fact that all of the lesions demonstrated a homogeneous contrast enhancement. Calcification or hypodense areas within the tumor matrix suggestive of cyst formation were found in 4 cases. No peritumoral edema was demonstrated. On angiograms, in all cases the tumors were visualized as hypervascular, space occupying mass lesions supplied by such feeding arteries as anterior and posterior choroidal, lenticulo-striate, thalamo-perforating, and pericallosal arteries. Among these arteries, either medial or lateral posterior choroidal arteries, or both, were commonly seen in these vascular tumors. Fine tumor vessels were also seen in the distal portion of these arteries. They were accompanied by a homogeneous tumor stain at either the late-arterial, capillary, or early-venous phase. PET images from a 21 year old female showed that the intraventricular tumor had an increased cerebral blood flow and volume at the tumor site, indicating a hypervascular tumor. However, this tumor was considered less malignant on the basis of its decreased rate of glycolysis, as evaluated by PET studies with 18-F-deoxyglucose. Lateral ventricular oligodendrogliomas, synonymously termed 'midline oligodendrogliomas,' have fairly specific neuroradiological features different from those of hemispheric oligodendrogliomas.

  5. Intratumoral distribution of CU-ATSM and FDG: immunohistochemical characterization of the region with high CU-ATSM or FDG accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Takako, Furukawa; Tsuneo, Saga; Yasuhisa, Fujibayashi [Institute of Radiological Sciences, Dept. of Diagnostic Imaging, Molecular Imaging Center, Nationa, Chiba (Japan); Takako, Furukawa; Takeshi, Tanaka; Yasuhisa, Fujibayashi [Fukui Univ., Biomedica Imaging Research Center (Japan)

    2006-07-01

    Intratumoral distribution of [Cu-64]Cu-di-acetyl-bis (N4-methyl-thio-semi-carbazone ) ({sup 64}Cu-ATSM) and fluorine-18 2-fluoro-2-deoxyglucose ({sup 18}FDG) in mice bearing tumors of four different origins, LLC1 (Lewis lung carcinoma), Meth-A (sarcoma), B16 (melanoma) and colon26 (adenocarcinoma), were compared to the immunohistochemical staining for proliferating cells (Ki67), blood vessels (CD34 or von Willebrand Factor (vWF)) and apoptotic cells (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method). With all the cell lines, {sup 64}Cu-ATSM and {sup 18}FDG were distributed to different regions of the tumor mass. The immunohistochemical study demonstrated that the high {sup 64}Cu-ASTM uptake regions were hypo-vascular and consisted of tumor cells arrested in cell cycle, while the high {sup 18}FGD uptake regions were hyper-vascular and consisted of proliferating cells. Through our study, it was revealed that one tumor mass contains two regions of different characteristics, which can be distinguished by {sup 64}Cu-ATSM and {sup 18}FDG. Since hypoxia and cell cycle arrest are critical factors to reduce the sensitivity of tumor to radiation and conventional chemotherapy, regions with such characteristics in tumor should be treated intensively as one of the primary targets. {sup 64}Cu-ATSM which can delineate hypoxic and cell cycle arrested regions in tumors can provide valuable information for cancer treatment as well as the possibility to treat such regions directly as an internal radiotherapy reagent. (author)

  6. Double-tracer autoradiography with Cu-ATSM/FDG and immunohistochemical interpretation in four different mouse implanted tumor models

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takeshi [Department of Otorhinolaryngology, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: wplants@mac.com; Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Fujieda, Shigeharu [Department of Otorhinolaryngology, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Kasamatsu, Shingo [Biomedical Imaging Research Center, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Yonekura, Yoshiharu [Biomedical Imaging Research Center, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: yfuji@fmsrsa.fukui-med.ac.jp

    2006-08-15

    Background: We studied the regional characteristics within tumor masses using PET tracers and immunohistochemical methods. Methods: The intratumoral distribution of {sup 64}Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([{sup 64}Cu]Cu-ATSM) and [{sup 18}F] 2-fluoro-2-deoxyglucose ({sup 18}F]FDG) in mice with tumors of four different origins (LLC1, Meth-A, B16 and colon26) was compared with the immunohistochemical staining of proliferating cells (Ki67), blood vessels (CD34 or von Willebrand factor), and apoptotic cells (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling method). Results: With all cell lines, [{sup 64}Cu]Cu-ATSM and [{sup 18}F]FDG were distributed with different gradation in the tumor mass. The immunohistochemical study demonstrated that the high [{sup 64}Cu]Cu-ATSM uptake regions were hypovascular and consisted of tumor cells arrested in the cell cycle, whereas the high [{sup 18}F]FDG uptake regions were hypervascular and consisted of proliferating cells. Conclusion: In our study, it was revealed that one tumor mass contained two regions with different characteristics, which could be distinguished by [{sup 64}Cu]Cu-ATSM and [{sup 18}F]FDG. Because hypoxia and cell cycle arrest are critical factors to reduce tumor sensitivity to radiation and conventional chemotherapy, regions with such characteristics should be treated intensively as one of the primary targets. [{sup 64}Cu]Cu-ATSM, which can delineate hypoxic and cell cycle-arrested regions in tumors, may provide valuable information for cancer treatment as well as possibly for treating such regions directly as an internal radiotherapy reagent.

  7. Measures of the inflammatory response in cryptogenic fibrosing alveolitis

    International Nuclear Information System (INIS)

    Pantin, C.F.; Valind, S.O.; Sweatman, M.; Lawrence, R.; Rhodes, C.G.; Brudin, L.; Britten, A.; Hughes, J.M.; Turner-Warwick, M.

    1988-01-01

    Cryptogenic fibrosing alveolitis (CFA) is characterized by interstitial fibrosis and parenchymal inflammation. Eleven patients with CFA (10 proved by lung biopsy) were followed over 2 yr using clinical symptoms, radiographic change, and pulmonary function tests to adjust their treatment. Lung lavage, positron camera (PET) measurements of regional extravascular lung density (Dev), pulmonary blood volume (Vb), and the metabolic rate for 18F-deoxyglucose (MRglc), clearance of 99mTc-diethylenetriaminepentacetate (99mTc-DTPA) aerosol, and lung uptake of 67Ga were measured initially and at the end of the first year to give a profile of the inflammatory response. Compared with normal subjects, there was an increased percentage of neutrophils and eosinophils in the lung lavage, increased Dev (p less than 0.002) with no significant difference in Vb, increased MRglc (p less than 0.02), 99mTc-DTPA clearance (p less than 0.002), and 67Ga uptake (p less than 0.02). The smallest increases in Dev were seen in the two patients with most destruction shown by lung biopsy. There were inverse correlations between Dev and both FVC and TLC, but a direct correlation between Vb and transfer factor. 99mTc-DTPA clearance changed concordantly with clinical status and radiographic and respiratory function changes during the first year. If glucose utilization (MRglc) remained in the normal range between the initial and first yearly assessment, the patient improved or remained stable during the second year as shown by clinical status and radiographic and respiratory function measurements. If it rose or remained high, the patient's condition deteriorated

  8. Discovery of biaryl-4-carbonitriles as antihyperglycemic agents that may act through AMPK-p38 MAPK pathway.

    Science.gov (United States)

    Goel, Atul; Nag, Pankaj; Rahuja, Neha; Srivastava, Rohit; Chaurasia, Sumit; Gautam, Sudeep; Chandra, Sharat; Siddiqi, Mohammad Imran; Srivastava, Arvind K

    2014-08-25

    A series of functionalized biaryl-4-carbonitriles was synthesized in three steps and evaluated for PTP-1B inhibitory activity. Among the synthesized compounds, four biaryls 6a-d showed inhibition (IC50 58-75 μM) against in vitro PTP-1B assay possibly due to interaction with amino acid residues Lys120, Tyr46 through hydrogen bonding and aromatic-aromatic interactions, respectively. Two biaryl-4-carbonitriles 6b and 6c showed improved glucose tolerance, fasting as well as postprandial blood glucose, serum total triglycerides, and increased high-density lipoprotein-cholesterol in SLM, STZ, STZ-S and C57BL/KsJ-db/db animal models. The bioanalysis of 4'-bromo-2,3-dimethyl-5-(piperidin-1-yl)biphenyl-4-carbonitrile (6b) revealed that like insulin, it increased 2-deoxyglucose uptake in skeletal muscle cells (L6 and C2C12 myotubes). The compound 6b significantly up-regulated the genes related to the insulin signaling pathways like AMPK, MAPK including glucose transporter-4 (GLUT-4) gene in muscle tissue of C57BL/KsJ-db/db mice. Furthermore, it was observed that the compound 6b up-regulated PPARα, UCP2 and HNF4α, which are key regulator of glucose, lipid, and fatty acid metabolism. Western blot analysis of the compound 6b showed that it significantly increased the phosphorylation of AMPK and p38 MAPK and ameliorated glucose uptake in C57BL/KsJ-db/db mice through the AMPK-p38 MAPK pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression.

    Science.gov (United States)

    Fenoy, Albert J; Schulz, Paul E; Selvaraj, Sudhakar; Burrows, Christina L; Zunta-Soares, Giovanna; Durkin, Kathryn; Zanotti-Fregonara, Paolo; Quevedo, Joao; Soares, Jair C

    2018-06-04

    Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18 F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

  10. Metabolic response to optic centers to visual stimuli in the albino rat: anatomical and physiological considerations

    International Nuclear Information System (INIS)

    Toga, A.W.; Collins, R.C.

    1981-01-01

    The functional organization of the visual system was studied in the albino rat. Metabolic differences were measured using the 14 C-2-deoxyglucose (DG) autoradiographic technique during visual stimulation of one entire retina in unrestrained animals. All optic centers responded to changes in light intensity but to different degrees. The greatest change occurred in the superior colliculus, less in the lateral geniculate, and considerably less in second-order sites such as layer IV of visual cortex. The