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Sample records for 18f fluorodeoxy glucose

  1. [(18) F]-Fluorodeoxy-d-glucose uptake-positive seborrhoeic keratosis on positron emission tomography may result from high expression of glucose transporter.

    Kariya, T; Kato, Y; Kanzaki, A; Kanda, Y; Ohara, T; Tsuboi, R

    2016-07-01

    [(18) F]-Fluorodeoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) is known to be highly accurate in differentiating benign lesions from malignant lesions. In rare cases, benign tumours, viral infections and sarcoidosis of the skin have been reported to show FDG uptake, but the mechanism remains unclear. Here we report the first documented case of seborrhoeic keratosis (SK) showing increased FDG uptake. FDG PET-CT can be used to detect enhanced glycolysis of tumour cells by measuring increased levels of glucose transporters (GLUTs) indicative of higher glucose uptake. GLUT1 and GLUT3 expression in this case was compared with that in PET-negative SK and two normal skin samples using quantitative polymerase chain reaction with paraffin-embedded tissue. The expression of GLUT1 and GLUT3 was higher in PET-positive SK than in PET-negative SK or normal skin. More specifically, the expression of GLUT3 was observed only in the PET-positive case. This study revealed that high GLUT1 and GLUT3 expression in SK might be associated with the uptake of FDG. PMID:26801868

  2. Molecular mechanisms of enhanced [18F] fluorodeoxy glucose (FDG) uptake in isochemically injured myocardium: the role of glucose transporter and hexokinase expression. Final technical report for period August 1, 1993--November 30, 1997

    Brosius, F.C. III

    1999-08-01

    We determined that there were no regional differences in GLUT1 or GLUT4 expression in normal dog heart. We demonstrated that glucose uptake was relatively enhanced in regions of severe ischemia in this model. We showed that GLUT1 mRNA and polypeptide expression but not GLUT4 expression were substantially and significantly increased in both ischemic and nonischemic myocardial regions after 6 hours. We also found that GLUT4 translocation and glucose uptake induced by ischemia in perfused rat hearts were not inhibited by Wortmannin, a PI3 kinase inhibitor, whereas insulin-stimulatd increases in GLUT4 translocation and glucose uptake were inhibited. To determine whether some of the same phenomena occurred in humans with chronic myocardial ischemia, we investigated myocardial GLUT mRNA expression in 11 patients who underwent coronary artery bypass surgery. We have cultured neonatal rat cardiomyocytes and tested the effects of several factors including hypoxia and insulin.

  3. Hyperglycemia-induced stimulation of glucose transport in skeletal muscle measured by PET- [18F]6FDG and [18F]2FDG

    A physiologically based model proposed by our group has been developed to assess glucose transport and phosphorylation in skeletal muscle. In this study, we investigated whether our model has the ability to detect a glucose-induced increase in glucose transport in skeletal muscle. In particular, we used small-animal positron emission tomography (PET) data obtained from [18F]6-fluoro-6-deoxy-D-glucose ([18F]6FDG). A 2 h PET scan was acquired following a bolus injection of [18F]6FDG in rats currently under euglycemic or hyperglycemic conditions, while somatostatin was infused during both conditions in order to prevent a rise in the endogenous plasma insulin concentration. We were thus able to assess the effect of hyperglycemia per se. For a comparison of radiopharmaceuticals, additional rats were studied under the same conditions, using [18F]2-fluoro-2-deoxy-D-glucose ([18F]2FDG). When [18F]6FDG was used, the time-activity curves (TACs) for skeletal muscle had distinctly different shapes during euglycemic and hyperglycemic conditions. This was not the case with [18F]2FDG. For both [18F]6FDG and [18F]2FDG, the model detects increases in both interstitial and intracellular glucose concentrations, increases in the maximal velocity of glucose transport and increases in the rate of glucose transport, all in response to hyperglycemia. In contrast, there was no increase in the maximum velocity of glucose phosphorylation or in the glucose phosphorylation rate. Our model-based analyses of the PET data, obtained with either [18F]6FDG or [18F]2FDG, detect physiological changes consistent with established behavior. Moreover, based on differences in the TAC shapes, [18F]6FDG appears to be superior to [18F]2FDG for evaluating the effect of hyperglycemia on glucose metabolism in skeletal muscle. (paper)

  4. Process for the production of /sup 18/F-2-deoxy-2-fluoro-d-glucose

    Shiue, C.Y.; Salvadori, P.A.; Wolf, A.P.; Fowler, J.S.; MacGregor, R.R.

    Process is given for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding /sup 18/F-compound by the reaction of acetyl hypofluorite or the corresponding /sup 18/F-compound with 3,4,6-tri-0-acetyl-D-glucal followed by hydrolysis. Process includes the production of the hypofluorite compound at ambient temperature.

  5. Aspects of the production of 18F-2-deoxy-2-fluoro-D-glucose via 18F2 with a tandem Van de Graaf accelerator

    During deuteron irradiation of 100 psig neon containing 1-2% of elemental fluorine, the induced 18F partitions into three main fractions. About 50% remains in the passivated nickel target after elution of the gas mixture. Some of the gaseous 18F is capable of performing fluorination reactions and is presumed to be 18F2: the rest is a mixture of at least two unreactive gases, one of which behaves on gas chromatography like CF4. The ratio of reactive to unreactive gaseous 18F decreases with longer irradiation times but increases when the target gas is cooled to -30C during bombardment. Reaction of the presumed 18F2 with 4.5,6-triacetyl-D-glucal, essentially by the published method, yielded 18F-2-deoxy-2-fluoro-4,5,6-triacetyl-x-D-glucosyl fluoride and the corresponding β-D-mannosyl fluoride. These were separated either by column chromatography or preparative TLC, using plates with a pre-absorbent layer. Hydrolysis of the glucoyl fluoride gave 18F-2-deoxy-2-fluoro-D-glucose (18F-2FDG) with a decay-corrected yield of about 10% based on 18F trapped by the triacetylglucal. The 60 min organ distribution of 18F from 18F-2-FDG in tumor bearing rats was compared with the corresponding distribution after administration of 18F-3-deoxy-3-fluoro-D-glucose (18F-3FDG). Organ/blood ratios were uniformly higher for 18F-2FDG than for no carrier added 18F-3FDG; only heart, brain and thyroid had ratios greater than unity. Added carrier 3-FDG further lowered organ/blood ratios. The main conclusion drawn from this animal work is that 18F-3FDG is unlikely to rival 18F-2FDG for nuclear medicine studies, where high target /blood ratios (obtained by metabolic trapping as the sugar-6-phosphate) are necessary. However 18F-3FDG may be useful for estimating the concentration of free glucose in organs if further work confirms that it is an essentially non-metabolized analog of glucose. (author)

  6. PET radiochemistry: synthesis of 2-[18 F]-fluorine-2-deoxy-D-glucose

    The present work describes the method for the synthesis of the 2-[18F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

  7. Positron emitting 18F-2-deoxy-2-fluoro-D-glucose: potential hot new therapy

    Preclinical studies suggest that 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) kills breast cancer cells without significant marrow toxicity or parenchymal toxicity. Radiation dose calculations estimated from fluorodeoxyglucose positron emission tomography images in women with metastatic disease indicate that 18F-FDG should be a feasible and safe option in humans. Because the available radiotherapeutic agents, strontium 89 and samarium 153 provide palliation to a limited population of women with bony metastases, new radiopharmaceutical agents with broader applicability are needed. The development of 18F-FDG as the first positron-emitting radiotherapeutic has the potential to be an innovative treatment, not only in osteoblastic disease, but also in osteolytic disease and in soft tissue metastases

  8. 99m-Tc-ubiquicidin scintigraphy in diagnosis of knee prosthesis infection and comparison with F-18 fluorodeoxy-glucose positron emission tomography/computed tomography

    Total knee arthroplasty has witnessed a significant increase in recent years. Despite the advantages of this surgical procedure, it has some complications, the most serious of which is prosthetic infection. The discrimination of bacterial infections from sterile inflammatory processes is of great importance in the management of periprosthetic infection (PPI). Ubiquicidin (UBI) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. Tc99m-UBI has recently been reported to be a promising radiotracer for infection imaging. We report a case of left knee PPI diagnosed using 99mTc-UBI scintigraphy and compared with F-18 fluorodeoxy-glucose positron emission tomography

  9. Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical

    Qualitative and quantitative analytical technique of low-molecular components of chemical and radiation-chemical decomposition of 2-deoxy-2-[18F]fluoro-D-glucose, 2-[18F]FDG radiopharmaceutical was developed for its extended QC by HPLC with mass-spectrometric electro-spray ionisation detector (ESI MS). The analysis constituted from the LC on silica gel NH2 bonded column combined with MS, UV-VIS, refraction index and radiometric detectors, and TLC on silica gel and high-performance TLC (HPTLC) on silica gel NH2 bonded as at the LC column. Condition of analysis, the composition of mobile phase at HPLC and the regime of ESI MS were optimised on the maximal intensity of the signals of analytes, which were predicted for commercial 2-[18F]FDG and its decomposition products. A modern LC/MS system was demonstrated to be suitable not only for identification of unknown analytes, but also for complex analysis of solutes except [18F]F-. This was advantageous for the 2-[18F]FDG autoradiolysis assessment about which no data were published. For comparative purposes, were used a classic TLC on silica gel with mobile phase acetonitrile: water at 95:5 v/v, and HPTLC on NH2 modified silica gel like the LC column. Mobile phase was identical as by LC/MS method (acetonitrile: 4 mM aqueous solution of ammonium formate 80:20 v/v). Retention times of reference samples: fluorodeoxyglucose, glucose, mannose, arabinose, deoxyglucose, gluconic and glucuronic acids at HPLC were established. Equal composition of the inlet sample and mobile phase was found important to avoid increased background of the MS detector and asymmetry of the chromatographic peaks. Reference substance detectability was investigated for various detectors. Characteristic ions were established for the analytes under consideration. Optimal performance of the ESI MS detector was discovered in negative ions mode or single ion monitoring (SIM) regime. The most intensive signal was observed for all analyte molecules association

  10. Assessment of radionuclidic impurities in 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) routine production

    Marengo, Mario [Medical Physics Department, S. Orsola-Malpighi Hospital, Bologna (Italy)], E-mail: marengo@med.unibo.it; Lodi, Filippo [Nuclear Medicine Unit, S. Orsola-Malpighi Hospital, Bologna (Italy); Magi, Silvia; Cicoria, Gianfranco; Pancaldi, Davide [Medical Physics Department, S. Orsola-Malpighi Hospital, Bologna (Italy); Boschi, Stefano [Nuclear Medicine Unit, S. Orsola-Malpighi Hospital, Bologna (Italy)

    2008-03-15

    In this paper, radionuclidic impurities generated during the bombardment of [{sup 18}O]water in the routine production of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) were studied. In order to assess such impurities and the efficacy of purification methods through the different steps of the synthesis, samples of the target filters, purification columns, [{sup 18}O]water recovered after the synthesis, and the final solution was collected and their activities measured and analyzed by means of a gamma-ray spectrometry system. The data demonstrated that purification methods adopted for the synthesis provide the [{sup 18}F]FDG radionuclidically pure, as requested by the EU Pharmacopeia.

  11. Production process validation of 2-[18F]-fluoro-2-deoxy-D-glucose

    The main of validation of production process of 2-[18F]-fluoro-2-deoxi-D-glucose (FDG) was to check: A) equipment's and services implicated in the production process were correctly installed, well documented, and worked properly, and B) production of FDG was done in a repetitive way according to predefined parameters. The main document was the Validation Master Plan, and steps were: installation qualification, operation qualification, process qualification and validation report. After finalization of all tests established in qualification steps without deviations, we concluded that the production process was validated because is done in a repetitive way according predefined parameters (Au)

  12. Production process validation of 2-[18F]-fluoro-2-deoxy-D-glucose

    The aim of production process validation of 2-[18F]-fluoro-2-deoxi-D-glucose (FDG) was to check: A) equipments and services implicated in the production process were correctly installed, well documented, and worked properly, and B) production of FDG was done in a repetitive way according to predefined parameters. The main document was the Validation Master Plan, and steps were: installation qualification, operational qualification, performance qualification and validation final report. After finalization of all tests established in qualification steps without deviations, we concluded that the production process was validated because consistently produced FDG meeting its pre-determined specifications and quality characteristics (Au)

  13. Synthesis and purification of 2-deoxy-2-[18F]fluoro-D-glucose and 2-deoxy-2-[18F]fluoro-D-mannose: characterization of products by 1H- and 19F-NMR spectroscopy

    A procedure has been developed that allows the separation 2-deoxy-2-[18F]fluoro-D-glucose from 2-deoxy-2-[18F]fluoro-D-mannose employing selectively optimized ion-moderated partition chromatography. Both compounds can be obtained with a >98% chemical and radiochemical purity in about one half-life of 18F. Both the α- and β-anomers of both sugars were completely characterized by high-resolution 1H- and 19F-NMR spectroscopy. Various convenient preparation methods for 2-deoxy-2-[18F]fluoro-D-glucose were compared. (author)

  14. Metabolism of 18F-FDG (2-fluoro-2-deoxy-D-glucose) in tumor cells

    Tumor cell components obtained at 5 min, 1 hr and 3 hr after 18F-FDG injections were analyzed by radio-thin-layer chromatography (TLC). Major metabolites were 18F-FDG-phosphate and 18F-FDM-phosphate. 18F-FDM and three unidentified compounds were found as minor metabolites. Time course of the composition of metabolites are as follows; 18F-FDG-phosphate was 88% at 5 mm after injection, but decreased to 53% at 3 hr after. 18F-FDM-phosphate was increased to 38% at 3 hr after injection. In conclusion, 18F-FDG is promptly phosphorylated after transportation into cell, and then exists as FDG-phosphate or 18F-FDM-phosphate. These results support known FDG distribution and metabolism, and it is possible that we use the information accumulated until now employing FDG manufactured by commercial supply system. (author)

  15. Routine 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) myocardial tomography using a normal large field of view gamma-camera

    There is a recent need to study glucose metabolism of the heart in ischemic, as well as in hibernating or stunned myocardium, and compare it with that in perfusion studies. In non-positron emission tomography centers, positron imaging is possible with a standard Anger-type camera if proper collimation and adequate shielding of the camera crystal can be achieved. For the study with fast-decaying isotopes, seven-pinhole tomography (7PHT), a limited-angle method designed for transaxial tomography of the left ventricle using a nonrotating camera, is well suited, because projections are acquired simultaneously. Individual adjustment (patient supine) of the camera's view axis (CAx) with the left ventricular axis (LVAx) gives excellent results: sensitivity for CHD 82%, specificity 72% in a prospective 201TI study (48 patients, x-ray coronarography as reference). Good alignment of CAx with LVAx is also achieved with the patient prone in LAO in a hammock above the camera surface. In this setting additional lead shielding of the camera is possible using a table reinforced with 5 cm of lead with a central hole for the 7PH-collimator, which has a special lead inlay. This allows utilization of the 511 KeV emitter 18F-FDG, which with a half-life of 109 minutes, can be transported a reasonable distance from the production site. System sensitivity and resolution for 18F was found comparable to 201Tl, 99mTc, and 123I using a phantom. First clinical examinations after 201Tl stress/redistribution studies showed increased 18F-FDG uptake in ischemic heart segments, as well as in hibernating nonperfused or stunned myocardium

  16. PET radiochemistry: synthesis of 2-[{sup 18} F]-fluorine-2-deoxy-D-glucose; Radioquimica PET: sintesis de 2-[{sup 18} F]-fluor-2-desoxi-D-glucosa

    Lopez D, F.A.; Flores M, A.; Zarate M, A.; Romo, E. [Unidad PET-Ciclotron, Facultad de Medicina, UNAM, Ciudad Universitaria, 04510 Mexico D.F. (Mexico)

    2005-07-01

    The present work describes the method for the synthesis of the 2-[{sup 18}F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

  17. The stability of 2-[{sup 18}F]fluoro-deoxy-D-glucose towards epimerisation under alkaline conditions

    Meyer, G.-J.; Matzke, K.H. [Klinik fuer Nuklearmedizin der Medizinischen Hochschule Hannover, Hannover (Germany); Hamacher, K. [Institut fuer Nuklearchemie des Forschungszentrums Juelich, Juelich (Germany); Fuechtner, F.; Steinbach, J. [Institut fuer Bioanorganische und Radiopharmazeutische Chemie des Forschungszentrums Rossendorf, Dresden (Germany); Notohamiprodjo, G.; Zijlstra, S. [Institut fuer Molekulare Biophysik, Radiopharmazie und Nuklearmedizin des Herz-und Diabetes-Zentrums Nordrhein-Westfalen, Bad Oeynhausen (Germany)

    1999-07-01

    Alkaline hydrolysis of 1,3,4,6-tetraacetyl-2-[{sup 18}F]fluoro-deoxy-D-glucose in the course of 2-[{sup 18}F]fluoro-deoxy-D-glucose ({sup 18}FDG) synthesis offers special advantages over acidic hydrolytic procedures, because the reaction time is short and thermal requirements are very mild. In view of the possible epimerization of 2-[{sup 18}F]fluoro-deoxy-D-glucose a multi-centre study has been performed to check the safety of this method for routine production of {sup 18}FDG in view of the quality standards set by the European Pharmacopoeia. The study revealed that in using 0.33 M NaOH for the hydrolysis, a limitation of the reaction temperature to 40 deg. C and a restriction of the reaction time to 5 min represent reaction conditions, which reliably limit the epimerization of {sup 18}FDG to {sup 18}FDM to 0.5%. Regarding the quality requirements on FDG as set forth by pharmacopoeial standards, alkaline hydrolysis of the intermediate in routine {sup 18}FDG production is a safe and efficient reaction pathway, which furthermore obviates the requirement to check for other 2-substituted deoxy-D-glucose derivatives.

  18. Measurement of glucose metabolism in patients with dilated cardiomyopathy using positron emission tomography with 18F-FDG: Initial Experience

    Introduction: Fluorine18 deoxyglucose (18F-FDG) has been used in numerous studies to determine the cardiac rate of glucose metabolism in normal and pathological conditions. It is known that during heart failure the metabolic pattern is altered. Patlack's graphical analysis allows the assessment of heart muscle glucose consumption in patients with non-ischaemic heart failure and normal subjects. Methods: Standardized measurement of glucose metabolism was performed in four patients with dilated cardiomyopathy and three healthy subjects. All subjects received an oral load of carbohydrates (75gr) previous to scanning. Dynamic images of the thorax were acquired. Myocardial uptake was estimated from time-activity curves in the atrium and left ventricle using Patlack's graphical analysis. Results: All subjects studied were male. 18F-FDG uptake rate for the group with dilated cardiomyopathy was 1.31±0.2, versus 1.26±0.37 ml/100gr/min in the control group. Conclusion: Measurement of cardiac glucose metabolism by 18F-FDG PET is feasible in a clinical service, allowing impact evaluation of physiologic and metabolic changes in the myocardium in different pathologic scenarios in addition to therapy assessment

  19. Experimental study for cancer diagnosis with positron-labeled fluorinated glucose analogs: [18F]-2-fluoro-2-deoxy-D-mannose

    18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65+-0.61% dose 18F-FDG/g and 2.65+-0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance of both 18F-FDG and 18F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas. Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM, which is a by-product of 18F-FDG synthesis, was also an excellent cancer diagnostic agent as well as 18-F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET. (orig.)

  20. Correlation of BRAFV600E Mutation and Glucose Metabolism in Thyroid Cancer Patients: An 18F-FDG PET Study

    Nagarajah, James; Ho, Alan L.; Tuttle, R. Michael; Weber, Wolfgang A.; Grewal, Ravinder K.

    2016-01-01

    There is significant interest in a better understanding of the genetic underpinnings of the increased glucose metabolic rates of cancer cells. Thyroid cancer demonstrates a broad variability of 18F-FDG uptake as well as several well-characterized oncogenic mutations. In this study, we evaluated the differences in glucose metabolism of the BRAFV600E mutation versus BRAF wild-type (BRAF-WT) in patients with metastatic differentiated thyroid cancer (DTC) and poorly differentiated thyroid cancer (PDTC). Methods Forty-eight DTC and 34 PDTC patients who underwent 18F-FDG PET/CT for tumor staging were identified from a database search. All patients were tested for the BRAFV600E mutation and assigned to 1 of 2 groups: BRAFV600E mutated and BRAF-WT. 18F-FDG uptake of tumor tissue was quantified by maximum standardized uptake value (SUVmax) of the hottest malignant lesion in 6 prespecified body regions (thyroid bed, lymph nodes, lung, bone, soft tissue, and other). When there were multiple lesions in 1 of the prespecified body regions, only the 1 with the highest 18F-FDG uptake was analyzed. Results In the DTC cohort, 24 tumors harbored a BRAFV600E mutation, whereas 24 tumors were BRAF-WT. 18F-FDG uptake of BRAFV600E-positive lesions (median SUVmax, 6.3; n = 53) was significantly higher than that of BRAF-WT lesions (n = 39; median SUVmax, 4.7; P = 0.019). In the PDTC group, only 5 tumors were BRAFV600E-positive, and their 18F-FDG uptake was not significantly different from the BRAF-WT tumors. There was also no significant difference between the SUVmax of all DTCs and PDTCs, regardless of BRAF mutational status (P = 0.90). Conclusion These data suggest that BRAFV600E-mutated DTCs are significantly more 18F-FDG–avid than BRAF-WT tumors. The effect of BRAFV600E on tumor glucose metabolism in PDTC needs further study in larger groups of patients. PMID:25814520

  1. Bilateral Tubo Ovarian Abscess Mimics Ovarian Cancer on MRI and 18F FDG PET/CT

    A 20 year old woman, who presented with a several week history of abdominal pain, was referred for magnetic resonance imaging (MRI) and 18F fluorodeoxy glucose (FDG) positron emission tomography (PET)/computed tomography (CT) after an ultrasound showed complex cystic masses arising from both ovaries. The MRI and 18F FDG PET/CT imaging characteristics of the ovarian masses were strongly suspicious for malignancy, and the masses were surgically removed. Histopathological evaluation revealed a bilateral tuboovarian abscess, with no evidence of malignancy. This case highlights a potentially serious pitfall in the evaluation of suspicious pelvic masses by 18F FDG PET/CT, Whereby a complex bilateral tuboovarian abscess may mimic the PET/CT imaging characteristics of an ovarian or pelvic malignancy.

  2. Synthesis of 2-[18F]fluoro-2-deoxy-L-glucose and positron emission tomography studies in monkeys

    2-[18F]Fluoro-2-deoxy-L-glucose was synthesized from its trifluoromethanesulfonyl precursor. The precursor was prepared by selective acetylation and triflation of L-mannose. L-Mannose was first treated with acetic anhydride in the presence of a catalytic amount of perchloric acid and then reacted with phosphorus tribromide followed by aqueous sodium acetate to produce pure 1,3,4,6-tetra-O-acetyl-a-L-mannopyranose in 32% yield. This compound was treated with trifluoromethanesulfonic anhydride and pyridine in methylene chloride to form 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-a-L-mannopyranose in 77% yield. Nucleophilic substitution of the triflate with 18F- in the presence of Kryptofix 2.2.2. followed by acid hydrolysis produced 2-[18F]fluoro-2-deoxy-L-glucose with a radiochemical yield of 20-30% (EOS) within 90 min. Biodistribution studies in rats and PET imaging in Rhesus monkeys demonstrated that this sugar analog distributes in the extracellular space of most organs but is excluded from the CNS. (author)

  3. Measurement of glucose and 2-deoxy-2-[18F]fluoro-D-glucose transport and phosphorylation rates in myocardium using dual-tracer kinetic experiments

    To examine the use of 2-deoxy-2-[18F]fluoro-D-glucose (2-FDG) as a glucose analog for measuring glucose utilization rate in myocardium, dual-tracer kinetic experiments with 2-FDG and 2-[3H]glucose were performed in the perfused, isolated rabbit interventricular septum to measure simultaneously the transport and phosphorylation rates of glucose and 2-FDG. Results of the present study indicated that, in the septum, (i) the transport rate constants of 2-FDG and glucose were similar in magnitude, (ii) the phosphorylation rate constant for 2-FDG was about 60% of that of glucose, (iii) hypoxia caused an increase in phosphorylation rates of glucose and 2-FDG without affecting transport. 9 refs.; 1 figure; 3 tabs

  4. Use of fluorine-18 free of carrier for the synthesis of 2-[18 F]-fluoro-2-deoxy-d-glucose by nucleophilic substitution

    Preliminary studies on the synthesis of 2 - [18 F]-fluoro-2-deoxy-d-glucose (2 - [18 F]-FDG) were carried out by means of the nucleophilic method proposed by K. Hamacher and the 18 F obtained in the Nuclear Reactor TRIGA Mark III of the Nuclear Center of Mexico. For the control of radiochemical quality it was used the chromatography technique in paper and silica gel with 4 solvent systems. The identification of the marked species with 18 F was carried out by means of comparison of its Rf with the Rf of the obtained not radioactive species, using the same synthesis method. (Author)

  5. [18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer

    Takebayashi, Ryusuke; IZUISHI, KUNIHIKO; Yamamoto, Yuka; Kameyama, Reiko; Mori, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki

    2013-01-01

    Background The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake. Material and methods Fifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum stand...

  6. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for {sup 18}F-FDG imaging of myocardial inflammation in mice

    Thackeray, James T.; Bankstahl, Jens P.; Bengel, Frank M. [Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Wang, Yong; Wollert, Kai C. [Hanover Medical School, Department of Cardiology and Angiology, Hanover (Germany)

    2015-04-01

    Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols. C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40 min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3 days after permanent coronary artery occlusion. Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial {sup 18}F-FDG accumulation. Injection with 40 min uptake in awake mice resulted in a marked reduction of global myocardial {sup 18}F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1 %ID/g vs 30.2 ± 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5 %ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2 %ID/g, p < 0.001). In the inflammatory phase, 3 days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial {sup 18}F-FDG accumulation that was similar to that observed under ketamine/xylazine. Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In

  7. Associations between liver 18F fluoro-2-deoxy-D-glucose accumulation and various clinical parameters in a Japanese population. Influence of the metabolic syndrome

    Liver demonstrates a heterogeneous 18F fluoro-2-deoxy-D-glucose (18F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver 18F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data. 18F-FDG positron emission tomography (PET) imaging was performed in 101 consecutive subjects for cancer screening. Multiple stepwise regression analysis was used to define the best predictors of the liver standardized uptake value (SUV) among height, weight, waist circumference, body mass index (BMI), systolic and diastolic blood pressure, BG and other biochemical data, id est (i.e.), aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total protein, total bilirubin, and alkaline phosphatase. Furthermore, we evaluated the association between liver 18F-FDG uptake and the metabolic syndrome. The independent factors for increased liver 18F-FDG uptake (mean SUV >=2) were BMI (P18F-FDG uptake. In addition, the liver 18F-FDG uptake of metabolic syndrome subjects was significantly higher than that of a non-metabolic syndrome subjects. BMI was the strongest determinant of liver 18F-FDG uptake, and the liver 18F-FDG uptake of metabolic syndrome subjects was significantly higher than that of non-metabolic syndrome subjects. This result suggests that a subject with a high liver 18F-FDG uptake should be screened for the metabolic syndrome. (author)

  8. Quantification of tumour {sup 18}F-FDG uptake: Normalise to blood glucose or scale to liver uptake?

    Keramida, Georgia [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); University of Sussex, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Dizdarevic, Sabina; Peters, A.M. [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); Bush, Janice [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom)

    2015-09-15

    To compare normalisation to blood glucose (BG) with scaling to hepatic uptake for quantification of tumour {sup 18}F-FDG uptake using the brain as a surrogate for tumours. Standardised uptake value (SUV) was measured over the liver, cerebellum, basal ganglia, and frontal cortex in 304 patients undergoing {sup 18}F-FDG PET/CT. The relationship between brain FDG clearance and SUV was theoretically defined. Brain SUV decreased exponentially with BG, with similar constants between cerebellum, basal ganglia, and frontal cortex (0.099-0.119 mmol/l{sup -1}) and similar to values for tumours estimated from the literature. Liver SUV, however, correlated positively with BG. Brain-to-liver SUV ratio therefore showed an inverse correlation with BG, well-fitted with a hyperbolic function (R = 0.83), as theoretically predicted. Brain SUV normalised to BG (nSUV) displayed a nonlinear correlation with BG (R = 0.55); however, as theoretically predicted, brain nSUV/liver SUV showed almost no correlation with BG. Correction of brain SUV using BG raised to an exponential power of 0.099 mmol/l{sup -1} also eliminated the correlation between brain SUV and BG. Brain SUV continues to correlate with BG after normalisation to BG. Likewise, liver SUV is unsuitable as a reference for tumour FDG uptake. Brain SUV divided by liver SUV, however, shows minimal dependence on BG. (orig.)

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

    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

  10. Potential role of 18F-2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography imaging in patients presenting with generalized lymphadenopathy

    Generalized lymphadenopathy is a common and often vexing clinical problem caused by various inflammatory, infective and malignant diseases. We aimed to review briefly and highlight the potential role of 18F-2-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in such patients. 18F-FDG PET/CT can play an important role in the management of generalized lymphadenopathy. It can help in making an etiological diagnosis; can detect extranodal sites of involvement and employed for monitoring response to therapy

  11. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  12. Novel application of 2-[18F]fluoro-2-deoxy-D-glucose to study plant defenses

    Introduction: Since its first use in humans in 1976, 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) continues to serve as a tracer to measure tissue glucose metabolism in medical imaging. Here we demonstrate a novel use for this tracer to study glycoside biosynthesis in plants as a measure of plant response to defense induction. Methods: Coupling autoradiography with radio high-performance liquid chromatography analysis of tissue extracts, we examined the combined effects of leaf wounding and treatment using the potent plant defense hormone, methyl jasmonate (MeJA), to measure tracer distribution and tracer use in secondary defense chemistry in Arabidopsis thaliana. We hypothesized that competing sinks like roots and reproductive tissues, as well as vascular architecture, would impact the induction of phenolic defenses of the plant that make use of glucose in glycoside formation by altering distribution and metabolic utilization of 18FDG. Results: Our studies showed that leaf orthostichy defined the major route of 18FDG transport in both vegetative and reproductive plants when a single petiole was cut as the entry point for tracer introduction. However, when nonorthostichous leaves were damaged and treated with MeJA, 18FDG was transported in its intact form to these leaves 3 h later, where it was incorporated into phenolic glycosides. Conclusions: Our work demonstrates a new use for 18FDG in plant science with insights into carbohydrate allocation that contradict conclusions of previous studies showing transport of resources away from damaged sites.

  13. Metformin abolishes increased tumor (18)F-2-fluoro-2-deoxy-D-glucose uptake associated with a high energy diet.

    Mashhedi, Haider; Blouin, Marie-José; Zakikhani, Mahvash; David, Stéphanie; Zhao, Yunhua; Bazile, Miguel; Birman, Elena; Algire, Carolyn; Aliaga, Antonio; Bedell, Barry J; Pollak, Michael

    2011-08-15

    Insulin regulates glucose uptake by normal tissues. Although there is evidence that certain cancers are growth-stimulated by insulin, the possibility that insulin influences tumor glucose uptake as assessed by ( 18) F-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography (FDG-PET) has not been studied in detail. We present a model of diet-induced hyperinsulinemia associated with increased insulin receptor activation in neoplastic tissue and with increased tumor FDG-PET image intensity. Metformin abolished the diet-induced increases in serum insulin level, tumor insulin receptor activation and tumor FDG uptake associated with the high energy diet but had no effect on these measurements in mice on a control diet. These findings provide the first functional imaging correlate of the well-known adverse effect of caloric excess on cancer outcome. They demonstrate that, for a subset of neoplasms, diet and insulin are variables that affect tumor FDG uptake and have implications for design of clinical trials of metformin as an antineoplastic agent. PMID:21811094

  14. Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

    Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [18F]-2-fluoro-2-deoxy-D-glucose ([18F]-FDG). The biodistribution of [18F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [18F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [18F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter. In the absence of insulin, the blood glucose concentrations of wild-type mice (132±26 mg/dl) and IRS-1 knockout mice (134±18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [18F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [18F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice. Our results showed that IR significantly affected [18F]-FDG uptake in the heart in normal daily conditions. IR was associated with decreased [18F

  15. Age and sex differences in cerebral glucose consumption measured by pet using [18-F] fluorodeoxyglucose (FDG)

    Resting cerebral glucose metabolic rates (CMRglc) were measured in 23 subjects by PET using FDG. Subjects were divided into several groups (mean age +- S.D.) 5 young males (YM) (27 +- 6); 6 young females (YF)(33 +9); 5 elderly males (EM)(73 +- 5); 7 elderly females (EF)(69 +- 7). Additionally, from these groups 4 YM, 3YF, 5EM and 4EF were studied again within 6 weeks under identical conditions. CMRglc in the YF group again was significantly hider than YM (p 0.05). No obvious relationships of CMRglc to the phase of the menstrual cycle was found in this small group. There was a trend (p=0.06) toward a higher CMRglc in YF than EF. These results support the findings of higher CBF in YF versus YM. The differences between the results of Kuhl et al (J. Cereb. and a reduction of CMRglc with age was found in a mixed group of males and females (58and female), and where no age effect was found the males, are also resolved by these findings. The authors suggest that the apparent age effect, in females in this study, is principally a hormonal one

  16. Michaelis-Menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F]fluorodeoxyglucose

    In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (tau = K*1/K1) and phosphorylation (psi = k*3/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using tau and psi, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k*2 and k*3 from the model, thus limiting the parameters to K* [equivalent to K*1k*3/(k*2 + k*3)], K*1, and the cerebral vascular volume (Vo). In six healthy elderly men (aged 61 +/- 5 years), time-activity records of cerebral cortical regions were analyzed with tau = 1.1 and psi = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k*3). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variables with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k*2 and k*3

  17. The study on glucose metabolism of the brain of patients with Parkinson's disease using 18F-FDG PET

    Objective: To study glucose metabolism of the brain of patients with Parkinson's disease (PD) by PET, to investigate the imaging characteristics of 18F-FDG PET in Chinese patients with PD. Methods: 50 min after intravenous administration of 18F-FDG, brain scan was performed on 33 patients with PD and 32 age-matched healthy subjects. Semiquantitative analysis was applied to assess the metabolic function of the brain by the ratio of mean radioactivity of various cerebral lobes (substantia nigra, putamen, caudatum, thalamus, temporal lobe, frontal lobe, parietal lobe, occipital lobe, hippocampus) to cerebellum (Rcl/cb). PET scan was compared with MRI. Results: In healthy subjects PET scan showed clear and symmetrical distribution of radioactivity in the cerebral lobes. 96.97% of PD patients showed abnormal PET images, 30.30% of PD patients' MRI showed abnormal, but only 9.09% of that was special. The radioactivity ratio of cerebral lobes to cerebellum of PD patients in nigra-striatum dopaminergic system and cerebral lobes was significantly decreased than that in healthy subjects. The opposite nigra-striatum system and frontal lobe of the more serious sick limbs were significantly more hypo-metabolic than the same side cerebral lobes. The characteristic PET images of PD patients showed that asymmetrical substantia nigra hypometabolism in 93.94% of the PD cases, striatum, thalamus asymmetrical hypometabolism in 69.70% and 36.36% PD cases; slight asymmetrical increase of radioactivity in striatum and thalamus in 15.15% PD cases; cerebral lobes asymmetrical hypometabolism of temporal lobe in 51.52%, frontal in 39.39%, parietal in 15.15%, occipital in 9.09%, hippocampal in 45.46% PD cases; slight cerebral asymmetrical hypermetabolism in 9.09% PD cases. Conclusions: In addition to cerebral structural lesions in the brain, asymmetrical hypometabolism and slight hypermetabolism can be found in nigra-striatum dopaminergic system accompany with cerebral hypometabolism or slight

  18. Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method

    The [18F]fluorodeoxyglucose (FDG) scan method with positron emission computed tomography was used to determine patterns of local cerebral glucose utilization (LCMRglu) in 40 normal volunteer subjects aged 18 to 78 years. Throughout all the studies, each subject was quiet, without movement, with eyes open and ears unplugged, exposed only to ambient room light and sound. For the entire group, whole brain mean CMRglu was 26.1 +/- 6.1 mumol 100 g-1 min-1 (mean +/- SD, n . 40). At age 78, mean CMRglu was, on the average, 26% less than at age 18, an alteration of the same order as the variance among subjects at any age. The gradual decline of mean CMRglu with advancing age occurred at a faster rate than was reported for mean cerebral oxygen utilization, possibly due to increasingly altered pathways for glucose utilization, or to increasing oxidation of ketone bodies or other alternative substrates. Glucose utilization in the hemispheres was symmetrical and mean CMRglu of overall cortex, caudate, and thalamus was equal in individuals at all ages. The slopes of decline with age were similar when LCMRglu was averaged over zones corresponding to centrum semiovale, caudate, putamen, and frontal, temporal, parietal, occipital, and primary visual cortex. However, the metabolic ratio of superior frontal cortex to superior parietal cortex declined with age, possibly due to selective degeneration of superior frontal cortex or to differences between age groups in the sensory and cognitive response to the study. These results should be useful in distinguishing age from disease effects when the FDG scan method is used

  19. Decreased [18F]fluoro-2-deoxy-D-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

    Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells. Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG

  20. Effect of ginseng pretreatment on cerebral glucose metabolism in ischaemic rats using animal positron emission tomography (PET) and [18F]-FDG

    To investigate the effect of ginseng on damaged brain activity, we evaluated the cerebral metabolic rate of glucose (CMRglc) as a functional index in post-ischaemic rats and compared the results with those obtained after the administration of a ginseng extract. CMRglc was measured using high resolution animal positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG). The rats subjected to a 30-min occlusion showed a significant reduction of k3, the rate constant for phosphorylation of 18F-FDG by hexokinase, compared with the normal value. The ginseng pretreatment prevented the reduction in k3 and CMRglc caused by ischaemia. Although further investigation is needed to elucidate the mechanism of action, ginseng may be useful for prevention and treatment of ischaemia. © 1997 John Wiley & Sons, Ltd

  1. [18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

    Sarwal, A.; Hantus, S.

    2016-01-01

    Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed.

  2. 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography/computed tomography imaging in paediatric oncology

    John; Freebody; Eva; A; Wegner; Monica; A; Rossleigh

    2014-01-01

    Positron emission tomography(PET) is a minimally in-vasive technique which has been well validated for the diagnosis, staging, monitoring of response to therapy, and disease surveillance of adult oncology patients. Tra-ditionally the value of PET and PET/computed tomogra-phy(CT) hybrid imaging has been less clearly defined for paediatric oncology. However recent evidence has emerged regarding the diagnostic utility of these mo-dalities, and they are becoming increasingly important tools in the evaluation and monitoring of children with known or suspected malignant disease. Important indi-cations for 2-deoxy-2-(18F)fluoro-D-glucose(FDG) PET in paediatric oncology include lymphoma, brain tumours, sarcoma, neuroblastoma, Langerhans cell histiocytosis, urogenital tumours and neurofibromatosis type Ⅰ. This article aims to review current evidence for the use of FDG PET and PET/CT in these indications. Attention will also be given to technical and logistical issues, the description of common imaging pitfalls, and dosimetric concerns as they relate to paediatric oncology.

  3. Calibrated image-derived input functions for the determination of the metabolic uptake rate of glucose with [18F]-FDG PET

    Christensen, Anders Nymark; Reichkendler, Michala H.; Larsen, Rasmus; Auerbach, Pernille; Højgaard, Liselotte; Nielsen, Henning B.; Ploug, Thorkil; Stallknecht, Bente; Holm, Søren

    2014-01-01

    We investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (Km) from dynamic [18F]-FDG PET scans of the thigh. Our objective was to obtain nonbiased, low...

  4. Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro-2-deoxy-D-glucose

    Allal, Abdelkarim Said; Slosman, Daniel O.; Kebdani, Tayeb; Allaoua, Mohamed Ghoulem; Lehmann, Willy; Dulguerov, Pavel

    2004-01-01

    Tumor uptake of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) may relate to outcome in cancer patients. Pretreatment FDG uptake was evaluated as a predictor of local control (LC) and disease-free survival (DFS) in patients with head-and-neck cancer managed primarily either by radiotherapy (RT) or surgery.

  5. Dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography of liver tumours without blood sampling

    Keiding, S; Munk, O L; Schiøtt, K M;

    2000-01-01

    Positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is a useful diagnostic tool for the detection of tumours. Using dynamic FDG PET, net metabolic clearance of FDG, K, can be calculated by Gjedde-Patlak analysis of the time course of the radioactivity concentrations in...

  6. Effect of Toxoplasma gondii infection on glucose metabolism in the brain of pregnant rats by [18F]FDG microPET imaging

    Toxoplasma gondii (T. gondii) is a pathogenic protozoan parasite, infection of which in early pregnancy increases the risk of serious sequelae in fetus. The aim of this study is to investigate the effect of T. gondii infection on glucose metabolism in the brain of pregnant rats by microPET using 18F-fluorodeoxygulcose (18F-FDG) as the tracer. Thirty female SD rats were divided into the T. gondii infection and control group. After set for pregnancy, the body weight was assessed, T. gondii infection was identified by PCR, ELISA technology and immunohistochemistry, and glucose metabolism in brain of rats was monitored by microPET scan. Our results showed that brain glucose metabolism was significantly increased in T. gondii-infected group comparing to the control, indicating microPET scan is more sensitive to detect the abnormality than traditional measurements. In addition, bio-distribution of 18F-FDG in T. gondii-infected rats was assessed by using another twenty female SD rats, which has higher uptake of 18F-FDG at 30 min after injection in whole brain. Furthermore, the expression profile of GLUT1 was also higher in the brain of pregnant rats of the infected group. Therefore, microPET can be effectively applied to in vivo assessment of small animals and contributes to early diagnosis of T. gondii infection, which also assists in understanding birth defects caused by T. gondii infection. (author)

  7. Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical. Author-review of thesis

    A qualitative and quantitative analytical technique of low-molecular components of chemical and radiation-chemical decomposition of 2-deoxy-2-[18F]fluoro-D-glucose, 2-[18F]FDG radiopharmaceutical was developed for its extended quality control by HPLC with mass-spectrometric electro-spray ionisation detector (ESI MS). The analysis constituted from the liquid chromatography on silica gel NH2 bonded column combined with mass-spectrometric, UV-VIS, refraction index and radiometric detectors. A modern LC/MS system (Agilent 1100) was demonstrated to be suitable not only for identification of unknown analytes, but also for complex analysis of solutes except [18F]F-. This was advantageous for the 2-[18F]FDG autoradiolysis assessment about which no data were published. For comparative purposes, were used a classic thin layer chromatography (TLC) on silica gel with mobile phase acetonitril: water at 95:5 v/v, and HPTLC on NH2 modified silica gel like the LC column. Mobile phase was identical as by LC/MS method (acetonitril: 4 mM aqueous solution of ammonium formate 80:20 v/v). Retention times of reference samples: fluorodeoxyglucose, glucose, mannose, arabinose, deoxyglucose, gluconic and glucuronic acids at HPLC were established. Optimal performance of the ESI MS detector was discovered in negative ions mode or single ion monitoring (SIM) regime. The most intensive signal was observed for all analyte molecules association with formate anion HCOO- and also for negative ions of deprotonised molecules. All acids appeared in the form of their lactones. FDG and Glc exhibited tendency for formation of a mixed associate charged by HCOO- anion. On the amine bond silica gel HPTLC column, FDG is poorly separated from fluoride, which even in presence of Kryptofix 2.2.2 remains on the start like on the silica gel layer. At LC-MS Kryptofix provides a very well measurable signals of associates with NH4+ a H+ ions in positive mode of ESI MS. Concentration of (19F)FDG carrier in 2-[18F

  8. Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D2 receptor availability and amphetamine-induced turning behaviour. Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [18F]MK-9470, [18F]FDG and [11C]raclopride. Relative glucose metabolism and parametric CB1 receptor and D2 binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [18F]MK-9470 uptake, glucose metabolism and D2 receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p -5), while an increase for these markers was observed on the contralateral side (>5%, all p -4). [18F]MK-9470 binding was also increased in the cerebellum (p = 2.10-5), where it was inversely correlated to the number of ipsiversive turnings (p = 7.10-6), suggesting that CB1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p = 1.10-6). These data point to in vivo changes in endocannabinoid transmission, specifically for CB1 receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D2 and CB1 neurotransmission in the contralateral hemisphere. (orig.)

  9. Correlation of Glut-1 glucose transporter expression with [{sup 18}F]FDG uptake in non-small cell lung cancer

    Higashi, Kotaro; Wang, Xiao; Xu, Linfeng; Oguchi, Manabu; Taki, Suzuka; Tonami, Hisao; Yamamoto, Itaru [Department of Radiology, Kanazawa Medical University, Ishikawa (Japan); Ueda, Yoshimichi; Sakurai, Aya; Katsuda, Shogo [Department of Pathology, Kanazawa Medical University, Ishikawa (Japan); Murakami, Manabu [Medical Research Institute, Kanazawa Medical University, Ishikawa (Japan); Seki, Hiroyasu [Department of Radiology, Kanazawa Cardiovascular Hospital, Ishikawa (Japan); Nambu, Yoshihiro [Department of Internal Medicine, Division of Respiratory Disease, Kanazawa Medical University, Ishikawa (Japan)

    2000-12-01

    Positron emission tomography (PET) with [{sup 18}F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [{sup 18}F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [{sup 18}F]FDG PET was performed 40 min after i.v. injection of 185 MBq [{sup 18}F]FDG. For semi-quantitative analysis of [{sup 18}F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n=7) (2.86%{+-}7.56% and 1.25{+-}0.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%{+-}25.64%, P<0.0001, and 3.94{+-}1.93, P=0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47{+-}0.63; intensities 2 and 3, n=23, SUV 4.78{+-}2.13; P<0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01). Overexpression of Glut-1 correlated with high [{sup 18}F]FDG uptake. These findings suggest that Glut

  10. Significance of 18F-2-deoxy-2-fluoro-glucose accumulation in the stomach on positron emission tomography

    To explain the accumulation of 18F-2-deoxy-2-fluoro-glucose (18FDG) on positron emission tomography (PET) in the stomach and differences in its pattern, we focus on the accumulation pattern in association with endoscopic findings of the gastric mucosa and Helicobacter pylori (Hp) infection. Of 599 cases undergoing 18FDG-PET examinations, we retrospectively analyzed the pattern of 18FDG accumulation in the stomach, findings of upper gastrointestinal endoscopy, and Hp infection. The pattern of 18FDG accumulation was classified into three groups: localized accumulation only in the fornix (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group B, 49 patients), and no accumulation (Group C, 191 patients). Regarding the relation between Hp infection and 18FDG accumulation, Hp infection was positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with significant differences (p18FDG accumulation and gastric mucosal inflammation, when Groups A and B were compared with Group C, nearly half of the cases in the former groups had papular redness with a significantly higher frequency of redness and erosion. Three cases found to have malignant tumor were limited to the former groups. One mucosa-associated lymphoid tissue (MALT) lymphoma case was also found in the same group. Accumulation of 18FDG largely corresponded to mucosal inflammation including superficial gastritis and erosive gastritis, and therefore the main cause of non-specific 18FDG accumulation was considered to be inflammatory mucosa (mainly redness). The accumulation pattern was not associated with atrophic changes of the gastric mucosa or with Hp infection, but with mucosal inflammatory changes, including redness and erosion localized to the fornix. Accumulation of 18FDG in the stomach suggests a high probability of the presence of inflammatory change in the gastric mucosa forming a background for the development of cancer or malignant lymphoma, and thus requires further

  11. Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer

    Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5–1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15–0.17 cm) and large (more than 1 cm) tumors were treated with 2–4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy

  12. Synthesis of 2-deoxi-2[18F]fluoro-D-glucose and its precursors for human diagnostics

    The planned Debrecen PET center requires an intensive radiopharmaceutical development program. In the frame of this project 2-[18F]FDG, an important radiopharmaceutical in the PET technique was synthesized. In order to prepare the precursor 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (TATM) the standard preparation protocols were modified for achieving a better yield. Stereochemically pure 2-[18F]FDG was synthesized using high purity TATM and 18F produced by the MGC-20 E cyclotron. Beside the elaboration of the synthesis a detailed description is also given of the methods used for quality control of both TATM and 2-[18F]FDG. In addition to the usual conformational and configurational characterization of precursor compounds measured NMR parameters were also used to explore the anomeric structure of the acetylated sugar derivates. (author) 24 refs.; 4 figs.; 4 tabs

  13. Optimizing 18F-FDG PET/CT imaging of vessel wall inflammation: the impact of 18F-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels

    18F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aorticmeanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotidmeanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotidmeanTBRmax and carotidmeanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting. (orig.)

  14. Use of fluorine-18 free of carrier for the synthesis of 2-[{sup 18} F]-fluoro-2-deoxy-d-glucose by nucleophilic substitution; Uso del fluor-18 libre de portador para la sintesis de la 2-[{sup 18} F]-fluoro-2-deoxi-d-glucosa por sustitucion nucleofilica

    Garcia S, I.; Ramirez, F.M

    1990-11-15

    Preliminary studies on the synthesis of 2 - [{sup 18} F]-fluoro-2-deoxy-d-glucose (2 - [{sup 18} F]-FDG) were carried out by means of the nucleophilic method proposed by K. Hamacher and the {sup 18} F obtained in the Nuclear Reactor TRIGA Mark III of the Nuclear Center of Mexico. For the control of radiochemical quality it was used the chromatography technique in paper and silica gel with 4 solvent systems. The identification of the marked species with {sup 18} F was carried out by means of comparison of its Rf with the Rf of the obtained not radioactive species, using the same synthesis method. (Author)

  15. 18F-2-Deoxy-2-Fluoro-D-Glucose Positron Emission Tomography: Computed Tomography for Preoperative Staging in Gastric Cancer Patients

    Youn, Seok Hwa; Seo, Kyung Won; Lee, Sang Ho; Shin, Yeon Myung; Yoon, Ki Young

    2012-01-01

    Purpose The use of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography-computed tomography as a routine preoperative modality is increasing for gastric cancer despite controversy with its usefulness in preoperative staging. In this study we aimed to determine the usefulness of preoperative positron emission tomography-computed tomography scans for staging of gastric cancer. Materials and Methods We retrospectively analyzed 396 patients' positron emission tomography-computed tomography...

  16. Comparison of tumor volumes derived from glucose metabolic rate maps and SUV maps in dynamic 18F-FDG PET.

    Visser, E.P.; Philippens, M.E.P.; Kienhorst, L.; Kaanders, J.H.A.M.; Corstens, F.H.M.; Geus-Oei, L.F. de; Oyen, W.J.G.

    2008-01-01

    Tumor delineation using noninvasive medical imaging modalities is important to determine the target volume in radiation treatment planning and to evaluate treatment response. It is expected that combined use of CT and functional information from 18F-FDG PET will improve tumor delineation. However, u

  17. Appropriate uptake period for myocardial PET imaging with {sup 18}F-FDG after oral glucose loading; Optimaler Akquisitionszeitpunkt fuer die Herz-PET mit {sup 18}F-FDG nach oraler Glukosebelastung

    Brink, I.; Hentschell, M.; Hoegerle, S.; Moser, E. [Abt. Nuklearmedizin, Radiologische, Universitaetsklinik Freiburg (Germany); Nitzsche, E.U. [Abt. Nuklearmedizin und PET, Universitaetsklink Basel (Switzerland); Mix, M.; Schindler, T. [Div. of Nuclear Medicine and Biophysics, UCLA School of Medicine, Los Angeles, CA (United States)

    2003-02-01

    Aim: Identification of a rationale for the appropriate uptake period for myocardial {sup 18}F-FDG-PET imaging of patients with and without diabetes mellitus. Methods: In a subset of 27 patients, static 2D-PET examination was performed of patients with chronic coronary artery disease and known myocardial infarction. The patients fasted (at least 4 h) before examination. {sup 18}F-FDG (330 {+-} 20 MBq) was injected intravenously. The image quality was semiquantitativly determined by ROI-analysis and the myocardium-to-blood pool activity ratio (M/B) was calculated. I.) Scans 30, 60, and 90 min p. i. of 10 non-diabetic patients (60 g oral glucose loading one hour before FDG-injection, low-dose intravenous insulin bolus if necessary). II.) Scans 30, 60, and 90 min p. i. of 10 patients with known non-insulin dependent diabetes (20 g glucose, insulin bolus). III.) Scans 90 min p. i. of 7 patients with known non-insulin dependent diabetes and elevated fasting serum glucose level (140-200 mg/dl; insulin bolus, no glucose). Results: I.) The M/B ratio significantly increases in non-diabetic patients with the uptake time (30 min 1.95 {+-} 0.20; 60 min 2.96 {+-} 0.36; 90 min 3.78 {+-} 0.43). II.) In patients with non-insulin dependent diabetes the M/B ratio also significantly increases with uptake time. Compared to non-diabetic patients group II reached smaller M/B values (30 min 1.56 {+-} 0.10; 60 min 2.15 {+-} 0.14; 90 min 2.71 {+-} 0.19). III.) In the group of patients with elevated fasting serum glucose level (who only got insulin but no glucose loading) the M/B activity ratio 90 min p. i. was clearly inferior compared with diabetic patients after oral glucose loading and insulin administration (M/B 2.71 {+-} 0.19 versus 2.16 {+-} 0.07). Conclusions: In static myocardial viability PET studies with {sup 18}F-FDG an uptake time of 90 min yields image quality superior to that obtained after shorter uptake time. (orig.) [German] Ziel: Definition eines optimalen

  18. Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

    Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

    2014-01-01

    Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels

  19. Optimizing {sup 18}F-FDG PET/CT imaging of vessel wall inflammation: the impact of {sup 18}F-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels

    Bucerius, Jan [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); University Hospital, RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Mani, Venkatesh; Fayad, Zahi A. [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); Moncrieff, Colin [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Machac, Josef [Mount Sinai School of Medicine, Division of Nuclear Medicine, Department of Radiology, New York, NY (United States); Fuster, Valentin [Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); The Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid (Spain); Farkouh, Michael E. [Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); Mount Sinai School of Medicine, Cardiovascular Imaging Clinical Trials Unit, New York, NY (United States); Tawakol, Ahmed [Massachusetts General Hospital, Harvard University, Cardiac MR PET CT Program, Boston, MA (United States); Rudd, James H.F. [Cambridge University, Division of Cardiovascular Medicine, Cambridge (United Kingdom)

    2014-02-15

    {sup 18}F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values ({sub mean}SUV{sub max}), target-to-background ratios ({sub mean}TBR{sub max}) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic{sub mean}SUV{sub max} values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid{sub mean}TBR{sub max} values. Prescan glucose levels were negatively associated with aortic and carotid{sub mean}TBR{sub max} and carotid{sub mean}SUV{sub max} values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol

  20. Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

    Introduction: Chronically altered glucose metabolism interferes with 18F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in 18F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on 18F-FDG uptake in tumors and biodistribution in normal organ tissues. Methods: 18F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUVmax) of normal organs and the main tumor site was measured. Differences in SUVmax in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. Results: Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUVmax in muscle cells and fat, whereas the mean cerebral SUVmax was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. Conclusions: Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases

  1. Comparing 2-[18F]fluoro-2-deoxy-D-glucose and [68Ga]gallium-citrate translocation in Arabidopsis thaliana

    2-[18F]fluoro-2-deoxy-D-glucose (18FDG) is a glucose surrogate commonly used in clinical or animal imaging but rarely in plant imaging to trace glucose metabolism. Recently, 18FDG has been employed in plant imaging for studying photoassimilate translocation and glycoside biosynthesis. There is growing evidence that 18FDG could be used as a tracer in plant imaging studies to trace sugar dynamics. However, to confirm this hypothesis, it was necessary to show that the observed 18FDG distribution in an intact plant is an outcome of the chemical nature of the introduced radiotracer and not of the plant vascular architecture or radiotracer introduction method. Methods: In the present work, we fed 18FDG and [68Ga]gallium-citrate (68Ga-citrate) solution through mature Arabidopsis thaliana leaf and monitored subsequent radioactivity distribution using positron autoradiography. The possible route of radioactivity translocation was elucidated through stem-girdling experiments. We also employed a bi-functional positron emission tomography/computed tomography (PET/CT) modality to capture 18FDG radiotracer dynamics in one of the plants in order to assess applicability of PET/CT for 4-D imaging in an intact plant. Results: Autoradiography results showed that [18F] radioactivity accumulated mostly in roots and young growing parts such as the shoot apex, which are known to act as sinks for photoassimilate. [18F] radioactivity translocation, in this case, occurred mainly via phloem. PET/CT results corroborated with autoradiography. [68Ga] radioactivity, on the other hand, was mainly translocated to neighboring leaves and its translocation occurred via both xylem and phloem. Conclusion: The radioactivity distribution pattern and translocation route observed after 18FDG feeding is markedly different from that of 68Ga-citrate. [18F] radioactivity distribution pattern in an intact plant is found similar to the typical distribution pattern of photoassimilates. Despite its limitations in

  2. Clinical Usefulness of :18F 2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Scan in the Diagnosis of Ampullary Carcinoma

    To evaluate the clinical usefulness of the 18F 2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) scan in the diagnosis of the ampulla of Vater cancer. CT images of 39 patients with ampulla of Vater cancer were reviewed regarding the lesion size, location, and bile or pancreatic duct dilatation. The patients were divided into three groups according to the lesion visibility on CT (Group A: visible mass, Group B: no visible mass but prominent ampulla, Group C: no visible lesion). Standardized uptake value (SUV) was measured on PET scan and the detection rate on PET images was comparable with that of CT images. Twenty-four patients (61.5%) were classified as Group A, 11 (28.2%) as Group B and 4 (10.3%) as Group C. All of Group A, 10 (90.9%) of Group B and 3 (75.0%) of Group C showed biliary dilatation. Pancreatic duct dilatation was shown in 18 (75.0%) of Group A, 9 (81.8%) of Group B, and 1 (25.0%) of Group C. The average of SUV of all patients was 5.90 ± 3.1. Most (94.9%) of all patients showed high FDG uptake over 2.5 with 93.9% in Group B and C. '18F-FDG PET scan was use for the detection of ampulla of Vater cancer, even though the lesion was invisible on CT.

  3. Routine use of dual time 18F-FDG PET for staging of preoperative lung cancer. Does it affect clinical management?

    The objective of this study was to compare the diagnostic accuracy of dual-time-point 18F-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) to single-time-point 18F-FDG PET for staging of preoperative lung cancer. Between November 2008 and December 2009, 107 patients who were diagnosed as having lung cancer or strongly suspected of having lung cancer were enrolled. They underwent dual-time-point 18F-FDG PET following conventional imaging. Dual-time-point 18F-FDG PET imaging (whole body) was performed at 1-h (early) post-FDG injection and repeated (2 h delayed) after injection. The diagnostic accuracy of pre-PET staging and post-PET staging was retrospectively evaluated, and the diagnostic accuracy of dual-time-point 18F-FDG PET was compared to that of single-time-point 18F-FDG PET. In 100 patients, the early 18F-FDG PET scan resulted in upstaging of the tumor in ten (10%) and down-staging of the tumor in five (5%) compared to the conventional scan. The delayed phase of 18F-FDG PET provided no additional information on staging for lung cancer patients. The remaining seven patients were diagnosed as not having lung cancer. This study confirmed that dual-time-point 18F-FDG PET is useful for differential diagnosis between benign and malignant lesions, but has no major impact on staging and therapeutic management of patients with pathologically proven lung cancer. (author)

  4. Positron emission tomography with 2-deoxy-2-[18F]fluoro-d -glucose in patients with thyroid diseases : FDG PET in thyroid diseases

    2011-01-01

    The aim of this thesis was to contribute to the field of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in benign and malignant diseases of the thyroid gland. The primary method used was review of retrospectively or prospectively enrolled patients referred for FDG PET at the Mayo Clinic, Rochester, MN, USA. PET findings were compared with the results of all other imaging, laboratory results and clinical information, as well as, extensive recording of follow-up i...

  5. The use of C-18 SEP PAK cartridges to simplify routine production of 2-deoxy-2-[18F]fluoro-D-glucose

    The synthesis of 2-deoxy-2[18F]fluoro-D-glucose has been simplified by the use of C-18 SEP PAK cartridges. The fluorinated sugar produced from the reaction of acetyl hypofluorite and tri-acetyl glucal (TAG) was extracted from the neutralized reaction mixture with C-18 SEP PAK cartridges. The product was washed off the cartridge with diethyl ether and hydrolyzed by HCl. After hydrolysis the product was purified by passage through ion retardation resin, alumina and another C-18 cartridge. The radiochemical purity was 98% and the radiochemical yield was 28%, decay corrected to EOB, with a total synthesis time of 50 min from EOB. (author)

  6. {sup 18}F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

    Skovgaard, Dorthe [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Bispebjerg Hospital, Institute of Sports Medicine, Copenhagen, NV (Denmark); Kjaer, Michael [Bispebjerg Hospital, Institute of Sports Medicine, Copenhagen, NV (Denmark); El-Ali, Henrik [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Kjaer, Andreas [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Rigshospitalet, Department Clinical Physiology, Nuclear Medicine and PET, Center of Diagnostic Investigations, Copenhagen (Denmark)

    2009-05-15

    To investigate exercise-related glucose uptake in rat muscle and tendon using PET/CT and to study possible explanatory changes in gene expression for the glucose transporters (GLUT1 and GLUT4). The sciatic nerve in eight Wistar rats was subjected to electrostimulation to cause unilateral isometric contractions of the calf muscle. {sup 18}F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight rats were cut out and scanned separately (distance{>=}1 cm). Muscle contractions increased glucose uptake approximately sevenfold in muscles (p<0.001) and 36% in tendons (p<0.01). The ex vivo group confirmed the increase in glucose uptake in intact animals. GLUT1 and GLUT4 were expressed in both skeletal muscle and tendon, but no changes in mRNA levels could be detected. PET/CT can be used for studying glucose uptake in rat muscle and tendon in relation to muscle contractions; however, the increased uptake of glucose was not explained by changes in gene expression of GLUT1 and GLUT4. (orig.)

  7. 18F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

    To investigate exercise-related glucose uptake in rat muscle and tendon using PET/CT and to study possible explanatory changes in gene expression for the glucose transporters (GLUT1 and GLUT4). The sciatic nerve in eight Wistar rats was subjected to electrostimulation to cause unilateral isometric contractions of the calf muscle. 18F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight rats were cut out and scanned separately (distance≥1 cm). Muscle contractions increased glucose uptake approximately sevenfold in muscles (p<0.001) and 36% in tendons (p<0.01). The ex vivo group confirmed the increase in glucose uptake in intact animals. GLUT1 and GLUT4 were expressed in both skeletal muscle and tendon, but no changes in mRNA levels could be detected. PET/CT can be used for studying glucose uptake in rat muscle and tendon in relation to muscle contractions; however, the increased uptake of glucose was not explained by changes in gene expression of GLUT1 and GLUT4. (orig.)

  8. Stability study of 2-[18F]Fluoro-2-Deoxy-D-Glucose (18FDG) stored at room temperature by physicochemical and microbiological assays

    The most widely used radiopharmaceutical in the expanding medical imaging technology of Positron Emission Tomography (PET) is 2-[18F]fluoro-2-deoxy-D-glucose (18FDG). The increasing demand for 18FDG requires reliable production in large amounts. The synthesis of 18FDG is based on a nucleophilic substitution of the triflate-leaving group from the precursor, mannose triflate, in the presence of Crypt and 2.2.2, as a phase-transfer agent. After labeling, the removal of the acetyl protecting groups from resulting 2-[18F]fluoro-1,3,4,6-tetra-Oacetyl- D-glucose is performed by alkaline hydrolysis, followed by purification and final filtration (0.22 μm). It was reported that 18FDG decomposes in vitro, resulting in the degradation of the radiochemical purity with time. The aim of this study was to evaluate physicochemical and microbiological stability of 18FDG, stored at room temperature (15-30 deg C), at different time intervals. It was investigated how the quality of this radiopharmaceutical varies with time under the influence of environmental factors. 18FDG pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins and sterility were evaluated according to the United States Pharmacopeia 31th edition analytical methods and acceptance criteria. The results suggest that 18FDG has physicochemical and microbiological stability up to 10 hours after the end of synthesis, under experimental conditions. (author)

  9. Change in hexose distribution volume and fractional utilization of ( sup 18 F)-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

    Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S. (Univ. of Chicago, IL (USA))

    1990-02-01

    We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi (18F)-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM.

  10. Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

    We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

  11. Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study

    Lai, Xinsheng; Ren, Jie; Lu, Yangjia; Cui, Shaoyang; Chen, Junqi; Huang, Yong; Tang, Chunzhi; Shan, Baoci; Nie, Bingbing

    2016-01-01

    Objective To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Methods Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and 18F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0. Results Pre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism. Conclusions Needling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model. PMID:26654890

  12. Differentiation of FDG-avid loco-regional recurrent and compromised benign lesions after surgery for breast cancer with dual-time point F-18-fluorodeoxy-glucose PET/CT scan

    The objective of this study was to evaluate the ability of dual-time point F-18-fluorodeoxy-glucose (FDG) positron emission tomography (PET)/CT scans to differentiate FDG-avid loco-regional recurrent and compromised benign lesions after surgery for breast cancer. A total of 64 FDG-avid recurrent lesions (local tumor recurrence or lymph node metastases) in 52 patients and 38 FDG-avid compromised benign lesions after surgery in 37 patients were included in the study. FDG PET/CT study was performed at 60 and 120 min after intravenous injection of 3.5 MBq/kg FDG. The maximum SUV (SUVmax) on the early and delayed scans and the percent change of SUVmax (%ΔSUVmax) between the two time points were measured. The optimal differential parameter was determined by receiver-operating characteristic curve analysis. The average early SUVmax, delayed SUVmax and ΔSUVmax% were 4.9±2.6, 6.0±3.6 and 18.2%±18.8 in FDG-avid recurrent lesions, and 2.1±0.8, 1.8±1.0 and -17.8%±21.3 in FDG-avid benign lesions, respectively. Delayed SUVmax was significantly increased compared with early SUVmax in recurrent lesions (P2.5 and %ΔSUVmax>0%, with a sensitivity of 90.6%, specificity of 81.5%, accuracy of 87.2%, negative predictive value (NPV) of 89.2%, and positive predictive value (PPV) of 83.7%, which were better than the respective values obtained with the use of delayed SUVmax>2.5 alone or %ΔSUVmax>0% alone (P2.5 (P<0.005). This approach with SUVmax estimation appears to improve the differentiation between FDG-avid loco-regional recurrent of breast cancer and compromised benign lesions after surgery, since delayed scanning significantly enhances the difference in FDG uptake between these lesions. (author)

  13. Analysis of glucose metabolism in patients with diabetes mellitus by using functional images derived from 18F-FDG PET

    Functional images of K complex (KC) and regional myocardial glucose utilization rates (rMGU), derived from F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission computed tomography, were prepared. Using functional images obtained, myocardial glucose metabolism was examined in the fasting state, oral glucose loading (OG), and insulin clamp (IC) condition. The subjects were 10 patients with diabetes mellitus (DM), consisting of 8 with non-insulin dependent DM and 2 with insulin dependent DM, and 4 normal persons. Image quality, derived from both OG and IC approaches, was favorable in the normal group. In the groups of non-insulin dependent DM and insulin dependent DM patients, however, image quality was good with IC method but not with OG method. In the group of non-insulin dependent DM, rMGU derived by IC method was relatively high, but was significantly lower than that in the control group, suggesting a decreased function in glucose transporter. When using OG method, rMGU was even more decreased due to high blood sugar and low insulin. In the group of insulin dependent DM, both IC and OG approaches achieved the same rMGU as that in the control group, with the exception of KC derived by OG method that was decreased due to high blood sugar. In moderate or severe DM, myocardial viability seems to be difficult to evaluate because F-18-FDG uptake is decreased in the ischemic area associated with fasting high blood sugar. Mismatching between blood flow and metabolism is also difficult to detect due to high insulin or glucose load. Thus, myocardial viability should be evaluated in the condition of slightly loaded insulin by decreasing blood sugar. (N.K.)

  14. Background Colonic 18F-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography Is Associated with the Presence of Colorectal Adenoma

    Lee, Ko Eun; Yoon, Hai-Jeon; Chang, Ji Young; Son, Hyo Moon; Ryu, Min Sun; Kim, Seong-Eun; Shim, Ki-Nam; Jung, Hye-Kyung; Jung, Sung-Ae

    2016-01-01

    18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is used to evaluate various kinds of tumors. While most studies on PET findings of the colon focus on the colonic uptake pattern, studies regarding background colonic uptake on PET scan are rare. The purpose of this study was to identify the association between the background colonic uptake and the presence of colorectal adenoma (CRA), which is a frequent precancerous lesion. We retrospectively reviewed the medical records of 241 patients with gynecologic malignancy who had received PET or PET/computed tomography (CT) scan and colonoscopy at the same period as a baseline evaluation. Background colonic 18F-FDG uptake was visually graded and the maximal standardized uptake values (SUVmax) of 7 different bowel segments were averaged. In univariate analysis, older age at diagnosis (≥ 50 years, p = 0.034), overweight (BMI ≥ 23 kg/m², p = 0.010), hypercholesterolemia (≥ 200 mg/dL, p = 0.027), and high grade background colonic uptake (p = 0.009) were positively associated with the prevalence of CRA. By multiple logistic regression, high grade background colonic uptake was independently predictive of CRA (odds ratio = 2.25, p = 0.021). The proportion of CRA patients significantly increased as background colonic uptake grade increased from 1 to 4 (trend p = 0.015). Out of the 138 patients who underwent PET/CT, the proportion of CRA patients in the group with high SUVmax (> 2.25) was significantly higher than in the low SUVmax group (27.5% vs. 11.6%, p = 0.031). In conclusion, high grade of background colonic 18F-FDG uptake is significantly associated with the prevalence of CRA. PMID:27509022

  15. Assessment of diffuse Lewy body disease by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET)

    Lewy body disease is, after Alzheimer's disease, the second most common cause of senile degenerative dementia with progressive cognitive deterioration, fluctuation of cognitive and motoric functions and psychotic symptoms. It is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. The aim of this study was to measure the cortical glucose metabolism using FDG PET (2-[18F]fluoro-2-deoxy-D-glucose position emission tomography) compared to normal subjects. Five patients (5 m, mean age 75 y) with clinically suspected diffuse Lewy body disease (DLB) were studied with FDG PET. PET studies of the head were performed with a Siemens ECAT-ART PET-scanner with attenuation correction using 137-Cs point sources. We found the same distribution pattern of diffuse glucose hypometabolism in the entire cortical region with relative sparing of the primary sensory-motor cortex in all the patients. The few cases reported in the literature so far describe findings similar to ours. The pattern of diffuse glucose hypometabolism in the entire cortex including the occipital region seems to be a typical feature of DLB that is distinctive from dementia of Alzheimer's disease

  16. Stability study of 2-[{sup 18}F]Fluoro-2-Deoxy-D-Glucose ({sup 18}FDG) stored at room temperature by physicochemical and microbiological assays

    Ferreira, Soraya Z.; Silva, Juliana B. da; Waquil, Samira S.; Correia, Ricardo F. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos], e-mail: radiofarmacoscdtn@cdtn.br

    2009-07-01

    The most widely used radiopharmaceutical in the expanding medical imaging technology of Positron Emission Tomography (PET) is 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ({sup 18}FDG). The increasing demand for {sup 18}FDG requires reliable production in large amounts. The synthesis of {sup 18}FDG is based on a nucleophilic substitution of the triflate-leaving group from the precursor, mannose triflate, in the presence of Crypt and 2.2.2, as a phase-transfer agent. After labeling, the removal of the acetyl protecting groups from resulting 2-[{sup 18}F]fluoro-1,3,4,6-tetra-Oacetyl- D-glucose is performed by alkaline hydrolysis, followed by purification and final filtration (0.22 {mu}m). It was reported that {sup 18}FDG decomposes in vitro, resulting in the degradation of the radiochemical purity with time. The aim of this study was to evaluate physicochemical and microbiological stability of {sup 18}FDG, stored at room temperature (15-30 deg C), at different time intervals. It was investigated how the quality of this radiopharmaceutical varies with time under the influence of environmental factors. {sup 18}FDG pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins and sterility were evaluated according to the United States Pharmacopeia 31{sup th} edition analytical methods and acceptance criteria. The results suggest that {sup 18}FDG has physicochemical and microbiological stability up to 10 hours after the end of synthesis, under experimental conditions. (author)

  17. Crossed cerebellar diaschisis. A positron emission tomography study with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose

    Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl-11C]methionine (MET) uptake is affected in CCD. In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017±0.023 and 0.014±0.039, respectively). Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity. (author)

  18. Validity of positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) in patients with renal cell carcinoma (preliminari report)

    Kawamura, Juichi; Hida, Shuichi; Yoshida, Osamu; Yonekura, Yoshiharu; Senda, Michio; Yamamoto, Kazutaka; Saji, Hideo; Fujita, Toru; Konishi, Junji.

    1988-10-01

    Positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) was carried out in 6 patients with renal tumors (5 renal cell carcinomas including one patient in whom the primary renal lesion was nephrectomized and 1 angiomyolipoma) and FDG accumulation was evaluated in the tumor lesion as a ''hot spot''. In dynamic images after 16 min. FDG accumulated in the tumor portion in 3 out of 4 patients with renal cell carcinoma. However, there was no accumulation in one renal cell carcinoma in which marked necrosis was histologically found. FDG accumulation was not evident in the tumorous lesion of angiomyolipoma. FDG accumulation was also noticed in the metastatic lesion of renal cell carcinoma in the liver or retroperitoneal lymph node. A gradual increase of FDG activity in the lesion of renal cell carcinoma was clearly demonstrated in the time-radioactivity curve, while activities rapidly decreased in renal cortex and pelvis, and liver. In the healthy portion of the kidney, FDG is filtered from the glomerulus and is not reabsorbed from the tubulus and is excreted in the collecting system. On the contrary, FDG, catalyzed by hexokinase, is phospholylated to FDG-6-phosphate which accumulates in the tumor tissue. PET using FDG can provide a new insight for understanding biological activity of renal cell carcinoma from the point of glucose metabolism in tumor tissue.

  19. Validity of positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in patients with renal cell carcinoma (preliminari report)

    Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was carried out in 6 patients with renal tumors (5 renal cell carcinomas including one patient in whom the primary renal lesion was nephrectomized and 1 angiomyolipoma) and FDG accumulation was evaluated in the tumor lesion as a ''hot spot''. In dynamic images after 16 min. FDG accumulated in the tumor portion in 3 out of 4 patients with renal cell carcinoma. However, there was no accumulation in one renal cell carcinoma in which marked necrosis was histologically found. FDG accumulation was not evident in the tumorous lesion of angiomyolipoma. FDG accumulation was also noticed in the metastatic lesion of renal cell carcinoma in the liver or retroperitoneal lymph node. A gradual increase of FDG activity in the lesion of renal cell carcinoma was clearly demonstrated in the time-radioactivity curve, while activities rapidly decreased in renal cortex and pelvis, and liver. In the healthy portion of the kidney, FDG is filtered from the glomerulus and is not reabsorbed from the tubulus and is excreted in the collecting system. On the contrary, FDG, catalyzed by hexokinase, is phospholylated to FDG-6-phosphate which accumulates in the tumor tissue. PET using FDG can provide a new insight for understanding biological activity of renal cell carcinoma from the point of glucose metabolism in tumor tissue. (author)

  20. Quantitative analysis of myocardial glucose utilization in patients with left ventricular dysfunction by means of {sup 18}F-FDG dynamic positron tomography and three-compartment analysis

    Morita, Koichi; Yoshinaga, Keiichiro; Mabuchi, Megumi; Kageyama, Hiroyuki; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Kita-ku, Sapporo (Japan); Katoh, Chietsugu; Kuge, Yuji [Hokkaido University Graduate School of Medicine, Department of Tracer Kinetics, Kita-ku, Sapporo (Japan); Noriyasu, Kazuyuki; Tsukamoto, Takahiro [Hokkaido University Graduate School of Medicine, Department of Cardiovascular Medicine, Kita-Ku, Sapporo (Japan)

    2005-07-01

    Myocardial glucose utilization (MGU) is altered in various heart diseases. The aim of this study was to quantitatively assess regional myocardial glucose utilization in patients with left ventricular (LV) dysfunction by dynamic{sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET). A total of 18 subjects were studied, including ten with LV dysfunction (seven with idiopathic dilated cardiomyopathy and three with aortic regurgitation; NYHA II in 8 and III in 2) and eight healthy normal volunteers. Patients with diabetes mellitus were excluded. A dynamic PET study was performed for 40 min following the injection of 370 MBq of FDG after 50-g glucose loading. On the basis of a three-compartment model, MGU, K{sub 1}, k{sub 2}, and k{sub 3} were computed on a pixel by pixel basis to generate LV myocardial parametric maps. FDG standardized uptake value (SUV) was also calculated using static images obtained 40 min after FDG injection. These metabolic values were compared with myocardial flow distribution (%Flow), LVEF, LV volumes, and LV wall thickening (WT) determined by gated myocardial single-photon emission computed tomography using QGS software in eight myocardial segments. MGU correlated positively with LV volumes and negatively with LVEF. K{sub 1} was significantly higher in the segments of the patients than in those of the normal volunteers (0.082{+-}0.055 vs 0.041{+-}0.017 ml min{sup -1} g{sup -1}, p<0.05), although there was no difference in MGU between the groups. On the other hand, SUV, k{sub 2}, and k{sub 3} did not differ significantly between the groups. Among the patients, the K{sub 1} values were significantly higher in the areas with impaired WT (%WT<17%) (0.109{+-}0.063 vs 0.069{+-}0.062 ml min{sup -1} g{sup -1}, p<0.05) and in the areas with flow reduction (%Flow<71%) (0.112{+-}0.076 vs 0.071{+-}0.046 ml min{sup -1} g{sup -1}, p<0.05). These results indicate that glucose utilization was preserved in the patients with LV dysfunction, mainly

  1. Development of a novel handheld intra-operative laparoscopic Compton camera for 18F-Fluoro-2-deoxy-2-D-glucose-guided surgery

    Nakamura, Y.; Shimazoe, K.; Takahashi, H.; Yoshimura, S.; Seto, Y.; Kato, S.; Takahashi, M.; Momose, T.

    2016-08-01

    As well as pre-operative roadmapping by 18F-Fluoro-2-deoxy-2-D-glucose (FDG) positron emission tomography, intra-operative localization of the tracer is important to identify local margins for less-invasive surgery, especially FDG-guided surgery. The objective of this paper is to develop a laparoscopic Compton camera and system aimed at use for intra-operative FDG imaging for accurate and less-invasive dissections. The laparoscopic Compton camera consists of four layers of a 12-pixel cross-shaped array of GFAG crystals (2× 2× 3 mm3) and through silicon via multi-pixel photon counters and dedicated individual readout electronics based on a dynamic time-over-threshold method. Experimental results yielded a spatial resolution of 4 mm (FWHM) for a 10 mm working distance and an absolute detection efficiency of 0.11 cps kBq‑1, corresponding to an intrinsic detection efficiency of  ∼0.18%. In an experiment using a NEMA-like well-shaped FDG phantom, a φ 5× 10 mm cylindrical hot spot was clearly obtained even in the presence of a background distribution surrounding the Compton camera and the hot spot. We successfully obtained reconstructed images of a resected lymph node and primary tumor ex vivo after FDG administration to a patient having esophageal cancer. These performance characteristics indicate a new possibility of FDG-directed surgery by using a Compton camera intra-operatively.

  2. Development of a novel handheld intra-operative laparoscopic Compton camera for (18)F-Fluoro-2-deoxy-2-D-glucose-guided surgery.

    Nakamura, Y; Shimazoe, K; Takahashi, H; Yoshimura, S; Seto, Y; Kato, S; Takahashi, M; Momose, T

    2016-08-01

    As well as pre-operative roadmapping by (18)F-Fluoro-2-deoxy-2-D-glucose (FDG) positron emission tomography, intra-operative localization of the tracer is important to identify local margins for less-invasive surgery, especially FDG-guided surgery. The objective of this paper is to develop a laparoscopic Compton camera and system aimed at use for intra-operative FDG imaging for accurate and less-invasive dissections. The laparoscopic Compton camera consists of four layers of a 12-pixel cross-shaped array of GFAG crystals ([Formula: see text] mm(3)) and through silicon via multi-pixel photon counters and dedicated individual readout electronics based on a dynamic time-over-threshold method. Experimental results yielded a spatial resolution of 4 mm (FWHM) for a 10 mm working distance and an absolute detection efficiency of 0.11 cps kBq(-1), corresponding to an intrinsic detection efficiency of  ∼0.18%. In an experiment using a NEMA-like well-shaped FDG phantom, a [Formula: see text] mm cylindrical hot spot was clearly obtained even in the presence of a background distribution surrounding the Compton camera and the hot spot. We successfully obtained reconstructed images of a resected lymph node and primary tumor ex vivo after FDG administration to a patient having esophageal cancer. These performance characteristics indicate a new possibility of FDG-directed surgery by using a Compton camera intra-operatively. PMID:27427184

  3. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival

  4. Detecting primary bladder cancer using delayed 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography imaging after forced diuresis

    The aim of this study was to evaluate the use of delayed pelvic 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography combined with the computed tomography (FDG-PET/CT) imaging, according to a standardized protocol including, pre-hydration and forced diuresis, for the detection of primary bladder cancer. We evaluated 38 consecutive patients with primary cT1-4 bladder cancer. They underwent standard FDG-PET/CT followed by delayed pelvic imaging after administration of 20 mg furosemide intravenously and extra oral water intake of 0.5 L. Two observers, blinded for patient data, scored both image sets for tumor visibility using a 3-point ordinal scale: (1) negative; (2) indeterminate; (3) positive. FDG-PET/CT findings were compared with histopathology and/or follow-up imaging. Our data suggest that delayed pelvic FDG-PET/CT imaging after forced detects more primary bladder tumors than standard EDG-PET/CT protocols. However, indeterminate bladder lesions on delayed PET/CT remain a problem and should be interpreted cautiously in order to avoid false positive results

  5. Early Treatment Response Monitoring Using 2-Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography Imaging during Fractionated Radiotherapy of Head Neck Cancer Xenografts

    Jiayi Huang

    2014-01-01

    Full Text Available Background. To determine the optimal timing and analytic method of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (PET imaging during fractionated radiotherapy (RT to predict tumor control. Methods. Ten head neck squamous cell carcinoma xenografts derived from the UT-14-SCC cell line were irradiated with 50 Gy at 2 Gy per day over 5 weeks. Dynamic PET scans were acquired over 70 minutes at baseline (week 0 and weekly for seven weeks. PET data were analyzed using standard uptake value (SUV, retention index (RI, sensitivity factor (SF, and kinetic index (Ki. Results. Four xenografts had local failure (LF and 6 had local control. Eighty scans from week 0 to week 7 were analyzed. RI and SF after 10 Gy appeared to be the optimal predictors for LF. In contrast, SUV and Ki during RT were not significant predictors for LF. Conclusion. RI and SF of PET obtained after the first week of fractionated RT were the optimal methods and timing to predict tumor control.

  6. Glucose metabolic change after visual and electrical stimulation of the rabbit retina using [18F]FDG PET: a preliminary result

    We studied to compare the cerebral cortical metabolic change after visual and electrical stimulation of the rabbit retina. Five PET scans were performed on five different days in an albino rabbit. One FDG PET study was done at rest state. In another two FDG PET studies, repetitive flash light stimulation (0.3 Hz, 6 min total) on each eye started 1 min prior to FDG injection and continued for 5 min into uptake. In the other two FDG studies, electrical retinal stimulation (500 μA, 1 Hz, 6 min total) of each eye using a suprachoroidal electrode placed under the visual streak was performed with the same procedure. Static PET data was acquired for 10 min after injection of [18F]FDG (37 MBq) through the catheter placed in the ear vein. All images were realigned to the rest state image. To remove the effects of global differences, each voxel value of the images was normalized versus mean value in whole brain. Change of cerebral glucose metabolism was examined with difference between rest and stimulation state. After visual and electrical stimulation of the rabbit retina, the cerebral area of increased metabolism could be determined. The hypermetabolic area of electrical stimulation overlapped with the area of visual stimulation, while electrically simulated cerebral area was focal and confined within the visually activated area. The electrical stimulation of the rabbit retina could increase the metabolism of the visual cortex which indicates electrical retinal stimulation caused visual perception of brain

  7. Glucose metabolic change after visual and electrical stimulation of the rabbit retina using [{sup 18}F]FDG PET: a preliminary result

    Kim, Su Jin; Lee, Jae Sung; Woo, Se Joon; Seo, Jong Mo; Chung, Hum; Lee, Dong Soo; Zhou, Zing Ai; Kim, Sung June [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We studied to compare the cerebral cortical metabolic change after visual and electrical stimulation of the rabbit retina. Five PET scans were performed on five different days in an albino rabbit. One FDG PET study was done at rest state. In another two FDG PET studies, repetitive flash light stimulation (0.3 Hz, 6 min total) on each eye started 1 min prior to FDG injection and continued for 5 min into uptake. In the other two FDG studies, electrical retinal stimulation (500 {mu}A, 1 Hz, 6 min total) of each eye using a suprachoroidal electrode placed under the visual streak was performed with the same procedure. Static PET data was acquired for 10 min after injection of [{sup 18}F]FDG (37 MBq) through the catheter placed in the ear vein. All images were realigned to the rest state image. To remove the effects of global differences, each voxel value of the images was normalized versus mean value in whole brain. Change of cerebral glucose metabolism was examined with difference between rest and stimulation state. After visual and electrical stimulation of the rabbit retina, the cerebral area of increased metabolism could be determined. The hypermetabolic area of electrical stimulation overlapped with the area of visual stimulation, while electrically simulated cerebral area was focal and confined within the visually activated area. The electrical stimulation of the rabbit retina could increase the metabolism of the visual cortex which indicates electrical retinal stimulation caused visual perception of brain.

  8. Preparation of a fine powder of 2-deoxy-2-[18F]fluoro-D-glucose suitable for inhalation to diagnose lung diseases by means of PET

    Fine 2-deoxy-2[18F]fluoro-D-glucose (18FDG) powder was obtained by adding diethyl ether into a methyl alcohol solution of 18FDG and other sugar as seed. When micronized particles of sodium N-acetyl-neuraminate (Neu5Ac-Na) were used as seed crystals, particles containing 18FDG were obtained and 80% of them were smaller than 10μm in size. More than 60% of these crystals were 4-6μm in size. In a preclinical study of forced inhalation in a dog, the 18FDG fine powder was mainly distributed in the trachea. The radioactivity in the trachea then increased once and a gradual decrease followed. The radioactivity was transferred into the blood and radioactivity incorporation into the heart was observed. After a normal volunteer inhaled 18FDG dry powder aerosol, the radioactivity was found in the respiratory tract and the peripheral area of the lung by means of PET. Absorption and in vivo dynamics of the 18FDG were also analysed. (author)

  9. Standardized uptake value of 2-[(18)F] fluoro-2-deoxy-D-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy

    Allal, Abdelkarim Said; Dulguerov, Pavel; Allaoua, Mohamed Ghoulem; Haenggeli, Charles-André; El-Ghazi, El Abbes; Lehmann, Willy; Slosman, Daniel O.

    2002-01-01

    In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy.

  10. Non-invasive estimation of hepatic glucose uptake from [{sup 18}F]FDG PET images using tissue-derived input functions

    Kudomi, N.; Jaervisalo, M.J.; Borra, R.; Viljanen, A.; Viljanen, T.; Knuuti, J. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Kiss, J.; Savunen, T. [University of Turku, Department of Surgery, Turku (Finland); Iida, H. [National Cardiovascular Center-Research Institute, Department of Investigative Radiology, Advanced Medical Engineering Center, Suita, Osaka (Japan); Nuutila, P. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Iozzo, P. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); National Research Council, Institute of Clinical Physiology, Pisa (Italy)

    2009-12-15

    The liver is perfused through the portal vein and hepatic artery. Quantification of hepatic glucose uptake (HGU) using PET requires the use of an input function for both the hepatic artery and portal vein. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not practical in humans. The aim of this study was to develop and validate a new technique to obtain quantitative HGU by estimating the input function from PET images. Normal pigs (n = 12) were studied with [{sup 18}F]FDG PET, in which arterial and portal blood time-activity curves (TAC) were determined invasively to serve as reference measurements. The present technique consisted of two characteristics, i.e. using a model input function and simultaneously fitting multiple liver tissue TACs from images by minimizing the residual sum of square between the tissue TACs and fitted curves. The input function was obtained from the parameters determined from the fitting. The HGU values were computed by the estimated and measured input functions and compared between the methods. The estimated input functions were well reproduced. The HGU values, ranging from 0.005 to 0.02 ml/min per ml, were not significantly different between the two methods (r = 0.95, p < 0.001). A Bland-Altman plot demonstrated a small overestimation by the image-derived method with a bias of 0.00052 ml/min per g for HGU. The results presented demonstrate that the input function can be estimated directly from the PET image, supporting the fully non-invasive assessment of liver glucose metabolism in human studies. (orig.)

  11. 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

    Juliano; J; Cerci; Camila; C; G; Linardi; Luís; F; Pracchia; José; Soares; Junior; Evelinda; Trindade; Dominique; Delbeke; Rodrigo; J; Cerci; Robert; Carr; José; C; Meneghetti; Valeria; Buccheri

    2013-01-01

    AIM:To assess the prognostic value and risk classification improvement of metabolic staging(MS)with Initial2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography(FDG-PET)in initial staging of Hodgkin’s Lymphoma(HL)patients to predict 5 years overall survival(5y-OS)and event free survival(EFS).METHODS:A total of 275 patients were included in this retrospective study,155 patients were staged with conventional anatomical staging(AS),and 120 also submitted to MS(FDG-PET).Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS.Risk-adjusted models incorporated clinical risk factors,computed tomography and FDG-PET staging.RESULTS:During the follow up of 267 evaluated patients,220(122 AS and 98 MS)achieved complete remission after first-line therapy(median follow-up:70±29 mo),treatment failure occurred in 79 patients and 34 died.The 5y-EFS for early vs advanced disease in AS patients was 79.3%and 66.7%,and 85.6%and53.6%in MS patients,respectively(P<0.01).The5y-OS for early and advanced disease with AS was91.3%and 81.5%,and 97.5%and 80.7%for patients staged with MS,respectively.Cox proportional hazards analysis demonstrated that FDG-PET added signifcant prognostic information and improved risk prediction(P=0.02).CONCLUSION:Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL,with impact in 5y-EFS and OS.

  12. Defining Radiotherapy Target Volumes Using 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography: Still a Pandora's Box?

    Purpose: We discuss the effect of 18F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) data on target volume definition for radiotherapy planning. We compared the effect of various thresholding methods on the PET-based target volume vs. the standard CT-based tumor volume. Methods and Materials: Different thresholding methods were reviewed and compared to our PET-based gross tumor volume data obtained from a cohort of 31 non-small-cell lung carcinoma patients who had undergone preoperative PET/CT scans for staging. The feasibility and limitations of FDG-based PET/CT data on target volume delineation in radiotherapy planning have been demonstrated with frequently used approaches for target outlining such as the qualitative visual method and the fixed 15% or 40% of the maximal iso-uptake value threshold methods. Results: The relationship between PET-based and CT-based volumes generally suffers from poor correlation between the two image data sets, expressed in terms of a large statistical variation in gross tumor volume ratios, irrespective of the threshold method used. However, we found that the maximal signal/background ratios in non-small-cell lung carcinoma patients correlated well with the pathologic results, with an average ratio for adenocarcinoma, large cell carcinoma, and squamous cell carcinoma of 10.5 ± 3.5, 12.6 ± 2.8, and 14.1 ± 5.9, respectively. Conclusion: The fluctuations in tumor volume using different quantitative PET thresholding approaches did not depend on the thresholding method used. They originated from the nature of functional imaging in general and PET imaging in particular. Functional imaging will eventually be used for biologically tailored target radiotherapy volume definition not as a replacement of CT- or magnetic resonance imaging-based anatomic gross tumor volumes but with the methods complementing each other in a complex mosaic of distinct biologic target volumes.

  13. Pharmacokinetics and metabolism of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) in mammary tumors of antiestrogen-treated rats

    Attempts are being made to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) as a noninvasive marker of therapy response in malignant tumors. We studied rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinomas by measuring the differential absorption ratio (DAR) and the metabolites of FDG in tumor homogenates. Half the rats were treated with the antiestrogen toremifene for 14 days and half were untreated. The histology of the tumors was studied by morphometry. The animals were killed 15, 45 or 240 min after injection. Regardless of whether the rats received toremifene or not, the fractional change in tumor volume correlated better with the DAR at 15 min [r = 0.284 (untreated) and r = 0.721 (treated)] and at 240 min [r 0.932 (untreated)], than at 45 min [r = -0.137 (untreated) and r = 0.265 (treated)]. Inverse relations were found for the fraction of unmetabolized FDG and change in tumor volume [r = 0.070 (45 min) and r = -0.872 (240 min) for untreated tumors and r = -0.963 (15 min) and r = -0.715 (45 min) for treated tumors]. The DAR and the fraction of unmetabolized FDG correlated also [r = -0.420 (15 min), r = -0.647 (45 min) and r = -0.976 (240 min) for untreated tumors, and r = -0.963 (15 min) and r = -0.213 (45 min) for treated tumors]. No significant therapy-induced morphometrical changes were observed. These findings imply that the FDG-derived uptake of radioactivity (= DAR) does relate to the tumor's speed of growth shortly after injection and also after some time, but there is a time period in between (a 'twilight zone') when this correlation is poor. These findings may have implications for FDG-PET studies in cancer patients: the optimal imaging time may have to be reconsidered

  14. Assessment of infarct size by positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose: a new absolute threshold technique

    Chareonthaitawee, P.; Iozzo, Patricia [MRC, Clinical Sciences Centre, Imperial College School of Science Technology and Medicine, London (United Kingdom); Schaefers, K.; Stegger, L. [MRC, Clinical Sciences Centre, Imperial College School of Science Technology and Medicine, London (United Kingdom); Department of Nuclear Medicine, University of Muenster, Muenster (Germany); Baker, C.S.R.; Camici, Paolo G.; Rimoldi, Ornella [MRC, Clinical Sciences Centre, Imperial College School of Science Technology and Medicine, London (United Kingdom); National Heart and Lung Institute, Faculty of Medicine, Imperial College School of Science Technology and Medicine, London (United Kingdom); Turkheimer, F. [MRC, Clinical Sciences Centre, Imperial College School of Science Technology and Medicine, London (United Kingdom); Imaging Research Solutions Limited, Cyclotron Building, Hammersmith Hospital, London (United Kingdom); Banner, N.R.; Yacoub, Magdi [National Heart and Lung Institute, Faculty of Medicine, Imperial College School of Science Technology and Medicine, London (United Kingdom); Bonser, Robert S. [Department of Cardiopulmonary Transplantation, Queen Elizabeth Medical Centre, Birmingham (United Kingdom)

    2002-02-01

    Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [{sup 18}F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, y=0.94x +0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x +2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings. (orig.)

  15. Comparison of Five Segmentation Tools for 18F-Fluoro-Deoxy-Glucose-Positron Emission Tomography-Based Target Volume Definition in Head and Neck Cancer

    Purpose: Target-volume delineation for radiation treatment to the head and neck area traditionally is based on physical examination, computed tomography (CT), and magnetic resonance imaging. Additional molecular imaging with 18F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) may improve definition of the gross tumor volume (GTV). In this study, five methods for tumor delineation on FDG-PET are compared with CT-based delineation. Methods and Materials: Seventy-eight patients with Stages II-IV squamous cell carcinoma of the head and neck area underwent coregistered CT and FDG-PET. The primary tumor was delineated on CT, and five PET-based GTVs were obtained: visual interpretation, applying an isocontour of a standardized uptake value of 2.5, using a fixed threshold of 40% and 50% of the maximum signal intensity, and applying an adaptive threshold based on the signal-to-background ratio. Absolute GTV volumes were compared, and overlap analyses were performed. Results: The GTV method of applying an isocontour of a standardized uptake value of 2.5 failed to provide successful delineation in 45% of cases. For the other PET delineation methods, volume and shape of the GTV were influenced heavily by the choice of segmentation tool. On average, all threshold-based PET-GTVs were smaller than on CT. Nevertheless, PET frequently detected significant tumor extension outside the GTV delineated on CT (15-34% of PET volume). Conclusions: The choice of segmentation tool for target-volume definition of head and neck cancer based on FDG-PET images is not trivial because it influences both volume and shape of the resulting GTV. With adequate delineation, PET may add significantly to CT- and physical examination-based GTV definition

  16. Estudo do metabolismo da glicose na tuberculose pulmonar ativa utilizando a tomografia por emissão de pósitrons (18F-FDG PET Evaluation of glucose metabolism in active lung tuberculosis by positron-emission tomography (18F-FDG PET

    SIDNEY BOMBARDA

    2002-09-01

    Full Text Available Os métodos de imagem utilizados na avaliação da tuberculose pulmonar incluem a radiografia e a tomografia computadorizada do tórax. As imagens obtidas pelos métodos de medicina nuclear permitem estudos funcionais e metabólicos dos órgãos de interesse, através do uso de radiofármacos específicos. Alterações do metabolismo da glicose podem ser detectadas pela tomografia por emissão de pósitrons (PET utilizando-se o 18F-fluorodesoxiglicose (18F-FDG. Essas alterações estão presentes nas doenças neoplásicas, inflamatórias e infecciosas. A tuberculose é uma doença granulomatosa causada pelo Mycobacterium tuberculosis, que se utiliza de glicose como fonte de energia. Objetivo: O estudo do metabolismo da glicose na tuberculose pulmonar através da PET e sua comparação com a tomografia computadorizada de tórax. Material e métodos: Foram avaliados 20 pacientes portadores de tuberculose pulmonar. Todos foram submetidos à PET e à tomografia computadorizada de tórax, em até 30 dias após o início do tratamento. Resultados: Todos os pacientes apresentaram captação positiva do 18F-FDG na PET. Na tomografia computadorizada do tórax, todos os pacientes apresentaram sinais compatíveis com atividade de tuberculose. A sensibilidade dos dois métodos foi de 100%. Houve concordância entre os achados do 18F-FDG PET e da tomografia computadorizada (K = 0,27 e p Current methods to evaluate lung tuberculosis include chest radiography and computed tomography. Nuclear medicine imaging techniques are performed after administration of specific radiopharmaceuticals that accumulate in the organs of interest. Alterations of glucose metabolism can be observed by positron-emission tomography, using 18F-fluorodeoxyglucose (18F-FDG PET. These findings are present in the neoplasms, but also in inflammatory and infectious diseases. Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis , that uses glucose as an energy source

  17. Quality of 2-deoxy-2-[18 F]fluoro-D-glucose injection prepared by isotopic exchange of fluorine using anion exchange or liquid phase exchange catalysed with aminopolyether

    Regular production of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) for Czech and Slovak PET Centers started at our upgraded U-120 cyclotrone and radiopharmaceutical laboratory already in June 1997 when [18F]FDG started being produced for validation and then for clinical trials in the Czech Republic. After registering the product by the Czech State Institute for Drug Control in June 1999, distribution of [18F]FDG,injection, to hospitals was commenced. The older automatic equipment (MicroLab I) of General Electric Medical Systems (GEMS) used technology with nucleophilic substitution of precursor (1,3,4,6-tetra-O-acetyl-2-O-trifluormethansulfonyl-β-D-mannopyranose) dissolved in acetonitrile with [18F]fluoride absorbed on a solid anion exchanger modified with 4-(4-methylpiperidino) pyridine. We used this technology until March 2001, when it was substituted with more advanced technology, MicroLab II. Nucleophilic substitution in the new technology is catalysed with aminopolyether (Kryptofix) in a liquid phase. Benefits of the MicroLab II technology consist of significantly higher yield of synthesis and better radiochemical purity of the product. Those parameters for intermediate period in March 2001 when both technologies were used is presented, so the conditions for production were comparable. The MicroLab II technology brings much higher yield of synthesis while radiochemical purity of the product also increases to over 99%

  18. Evaluation of whole-body cancer screening using 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography. A preliminary report

    18F-2-deoxy-2-fluoro-d-glucose positron emission tomography (FDG-PET) is a promising screening modality targeting whole body. However, the validity of PET cancer screening remains to be assessed. Even the screening accuracy for whole-body screening using FDG-PET has not been evaluated. In this study, we investigated the screening accuracy of PET cancer screening. A total of 2911 asymptomatic participants (1629 men and 1282 women, mean age 59.79 years) underwent both FDG-PET and other thorough examinations for multiple organs (gastrofiberscopy, total colonofiberscopy or barium enema, low-dose thin section computed tomography and sputum cytology, abdominal ultrasonography, an assay of prostate-specific antigen, mammography, mammary ultrasonography, Pap smear for the uterine cervix, and magnetic resonance imaging for the endometrium and ovaries) between February 2004 and January 2005, and followed sufficiently. The detection rate, sensitivity, specificity, and positive predictive value of FDG-PET were calculated using cancer data obtained from all examinations along with a 1 year follow-up. From among 2911 participants FDG-PET found 28 cancers, 129 cancers were PET negative. PET-positive cancers comprised seven colorectal cancers, four lung cancers, four thyroid cancers, three breast cancers, two gastric cancers, two prostate cancers, two small intestinal sarcomas (gastrointestinal stromal tumors), one malignant lymphoma, one head and neck malignancy (nasopharyngeal carcinoid tumor), one thymoma, and one hepatocellular carcinoma. PET-negative cancers included 22 gastric cancers and 20 prostate cancers that were essentially difficult to detect using FDG-PET. The overall detection rate, sensitivity, specificity, and positive predictive value were estimated to be 0.96%, 17.83%, 95.15%, and 11.20%, respectively. FDG-PET can detect a variety of cancers at an early stage as part of a whole-body screening modality. The detection rate of PET cancer screening was higher than

  19. Positron emission tomography with 2-[18F]-Fluoro-2-Deoxy-D-Glucose for initial staging of hodgkin lymphoma: a single center experience in Brazil

    Juliano Julio Cerci

    2009-06-01

    Full Text Available BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS methods, including computed tomography (CT and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively. FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively. FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82 of the patients and downstaged 11% (9/82 of the patients. As a result of these changes in staging, 15% (13/82 of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients brought about by the addition of PET to the staging algorithm

  20. 18F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

    Skovgaard, Dorthe; Kjaer, Michael; El-Ali, Henrik;

    2009-01-01

    unilateral isometric contractions of the calf muscle. (18)F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight...

  1. Quality of 2-deoxy-2-[18F]fluoro-d-glucose injection prepared by isotopic exchange of fluorine using anion exchange or liquid phase exchange catalysed with amino polyether

    Production of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) for Czech and Slovak PET Centres started on our upgraded U-120 cyclotron and in our radiopharmaceutical laboratory as early as June 1997, first for validation purposes and subsequently for clinical trials. The product was registered by the Czech State Institute for Drug Control in June 1999, and then distribution of the [18F]FDG injection preparation to hospitals was launched. The older automatic equipment (MicroLab I) manufactured by General Electric Medical Systems (GEMS) was based on a technology involving nucleophilic substitution of the precursor (1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose) dissolved in acetonitrile with [18F]fluoride absorbed on a solid anion exchanger modified with 4-(4-methylpiperidino) pyridine. This technology was used by us until March 2001, when it was superseded by a more advanced technology, MicroLab II. The nucleophilic substitution in the new technology is catalysed with amino polyether (Kryptofix) in a liquid phase. Benefits of MicroLab II include a significantly higher yield and better radiochemical purity of the product

  2. Value of tumour marker S-100B in melanoma patients: a comparison to 18F-FDG PET and clinical data

    Aim: The S-100B protein is commonly used in the immunohistochemical diagnosis of malignant melanoma and its metastases and has recently been introduced as a tumor marker in peripheral blood, whereas 18F-FDG PET is currently the most sensitive in-vivo imaging method for melanoma staging. Thus, the efficiency of serum S-100B and 18F-FDG PET in the detection of metastatic disease in melanoma patients are compared. Methods: Serum S-100B was measured with a commercially available immunoradiometric assay. As part of primary tumour staging whole-body position emission tomography (PET) with 18F labeled fluorodeoxy-D-glucose (18F-FDG) was performed in 67 patients suffering from cutaneous melanoma with a tumour thickness > 0.75 mm and a Clark-level III-V. Final diagnosis based on histology, morphologic imaging results and/or clinical follow-up after at least six months. Results: No evidence of disease was seen in 43 of 67 patients (64.2%), 11 patients (16.4%) presented with lymph node metastases, 13 patients (19.4%) had one or more distant metastases. Altogether, 18 of 67 patients showed S-100B values > 0.2 μg/l, including two patients without metastatic disease, 3 of 11 patients with lymph node metastases, and the 13 patients with distant metastases. One patient showed false-positive FDG-uptake in the mediastinum, but presented with S-100B values off curve. Conclusion: Our data indicate that serum S-100B determination might be helpful in identifying melanoma patients with distant metastases. In comparison to 18F-FDG PET, the value of serum S-100B for lymph-node staging is limited. (orig.)

  3. Chilean experience in production of 18F-FDG from 18F in a reactor

    18F-FDG (fluorine-deoxy-D-glucose) is an important and useful radiopharmaceutical for imaging and study of myocardial viability. Usually cyclotron-produced 18F is used to label 18F-FDG. The availability of a 5 MW Nuclear Reactor in Chile and the absence of a quality cyclotron to produce 18F required that we developed a method in order to obtain suitable 18F to label 18F-FDG using the facilities we have at the Nuclear Center of La Reina, Chilean Nuclear Energy Commission. The nuclear reactions involved are: 6Li(n,aα)3H and 16O(3H,n)18F. Enriched Li2CO3 (6Li = 95 %) was irradiated in a 5 MW swimming pool type nuclear reactor with a neutron flux of 5. 7 x 1013 n cm-2 s-1 for 4 hours. The irradiated Li2CO3 was dissolved in H2SO4 (1:1) and distilled as trimethylsilyl(18F)fluoride (18F-TMS). The labelling of the sugar was carried out using the method described by Hamacker. The 18F-TMS was trapped in a solution of acetonitrile, water, potassium carbonate, and kriptofix and hydrolysed to form 18F fluoride. The nucleophilic complex reacts with 1,3,4,6, tetra-O-acetyl- 2-O-trifluoromethanesulfonyl-bβ-D-mannopyranose. The acetylated carbohydrate by acid hydrolysis produces 18F-FDG. The final product was purified using an ion retarding resin (AG11-A8) and a system two Sep Pak Plus: Alumina and C-18 cartridge and sterilised by Millipore 0.22 μm filter. The 18F-FDG was obtained in an apyrogenic and sterile solution. The 18F radionuclide purity was higher than 99.9% and the radiochemical purity ofthe18F-FDG obtained was over than 99%. Residual 3H content was as low as 20 (Bq 3H/MBq 18F-FDG.). The yield of the process 18F-FDG was 13.2 %. (authors)

  4. Chilean experience in production of 18F-FDG from 18F of reactor

    18F-FDG (fluorine-deoxy-D-glucose) is an important and useful radiopharmaceutical for imaging and study of miocardial viability. Usually cyclotron produced 18F is used to label 18F-FDG. Due to the availability of a 5MW Nuclear Reactor in Chile and the absence of a qualified Cyclotron to produce 18F we have developed a method in order to obtain suitable 18F to label 18F-FDG using the facilities we have at the Nuclear Center of La Reina, Chilean Nuclear Energy Commission. The nuclear reactions involved are: 6Li(n,alpha) 3H and 16O(3H,n)18F. Li-2CO-3, enrich (6Li =95%) was irradiated in a 5 MW swimming pool type Nuclear Reactor at a Neutron flux of 5.7x 1013 n cm-2sec-1during 4 hours. The irradiated Li-2CO-3 was dissolved in H-2SO-4(1:1) and distilled as trimethylsilyl (18F) fluoride (18F-TMS). The labelling of the sugar was carried out using the method described by Hamacker. The 18F-TMS was trapped in a solution of acetonitrile, water, potassium carbonate and kriptofix and hydrolysed to form 18F fluoride. The nucleofilic complex reacts with 1,3,4,6, tetra-O-acetyl-2-O-trifluormethanesulfonyl-beta-D-mannopyranose. The acetiled carbohydrate by acid hydrolysis produce 18FDG. The final product was purified using a ion retarding resin (AG11-A8) and a system a two Sep Pak Plus: Alumina and C-18 cartridge and sterilised by Millipore 0,22 um filter. The 18F-FDG was obtained in an apyrogenic and sterile solution. The 18F Radionucleidic Purity was higher than 99,9% and the Radiochemical Purity of the 18F-FDG obtained was over than 99%. Residual 3H content was as low as 20 (Bq3 H/MBq 18F-FDG). The yield of the process of 18F-FDG was 37 %. Studies in patient with recently myocardial disease have showed the successful of the 18F-FDG. The C.CH.E.N supports an active diagnostic nuclear cardiology program

  5. Multiple bone metastases detected on 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography in a breast cancer patient: Case report and literature review

    Zeki Dostbil

    2012-09-01

    Full Text Available Bone scintigraphy has been widely used to assess skeletal metastasis in patients with breast cancer. 18F-FDGPET/CT is another imaging modality that has gained previously wide use to determine metastasis based on increased glucose metabolism in malignant cells. Generally, these two modalities give similar results in evaluation of bone metastasis of breast cancer. In this breast cancer case, 99mTc-MDP bone scintigraphy showed normal findings in regards to skeletal metastasis while 18FFDG-PET/CT, contrast-enhanced CT and MRI revealed multiple metastatic focuses. J Clin Exp Invest 2012; 3 (3: 426-429Key words: 18F-fluorodeoxyglucose, bone metastasis, bone scintigraphy, positron emission tomography

  6. A prospective analysis of {sup 18}F-FDG PET/CT in patients with uveal melanoma: comparison between metabolic rate of glucose (MRglu) and standardized uptake value (SUV) and correlations with histopathological features

    Calcagni, Maria Lucia; Mattoli, Maria Vittoria; Rufini, Vittoria; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Institute of Nuclear Medicine, Roma (Italy); Blasi, Maria Antonietta; Sammarco, Maria Grazia [Universita Cattolica del Sacro Cuore, Institute of Ophthalmology, Roma (Italy); Petrone, Gianluigi; Mule, Antonino [Universita Cattolica del Sacro Cuore, Department of Pathology, Roma (Italy); Indovina, Luca [Universita Cattolica del Sacro Cuore, Physics Unit, Roma (Italy)

    2013-10-15

    To evaluate whether standardized uptake value (SUV) and/or metabolic rate of glucose (MRglu) are different among epithelioid, mixed, and spindle cell uveal melanomas, as well as between low and high risk melanomas; to correlate ultrasonographic data and metabolic parameters with histopathological features; and to assess the role of {sup 18}F-FDG PET/CT for evaluating prognosis. Of 34 eligible patients prospectively enrolled with clinical suspicion of medium/large uveal melanoma, 26 (15 men, mean age 62.8 {+-} 11.8 years) were evaluated. All patients underwent metastatic work-up, 3-D dynamic brain and whole-body {sup 18}F-FDG PET/CT, and surgery. Of the 26 ocular lesions, 23 showed {sup 18}F-FDG uptake, with a sensitivity of 88 %. MRglu was significantly higher in the epithelioid cell melanomas than in the spindle cell melanomas, as well as in high-risk lesions than in low-risk lesions (p = 0.01, p = 0.02, respectively). SUV and MRglu were correlated with histopathological features while ultrasonographic data were not. MRglu is useful for distinguishing the different cell types in uveal melanoma, as well as high-risk from low-risk lesions, while SUV is not. MRglu provides a more accurate evaluation of glucose consumption, whereas SUV provides only an estimation. In addition, the metabolic parameters correlate with histopathological features, well also reflecting cellular behaviour in ocular malignancy. A longer follow-up is needed to assess the role of {sup 18}F-FDG in evaluating prognosis. (orig.)

  7. The effect of lung cancer patients' weight, blood glucose concentration and lesion size of lung cancer on 18F-FDG PET/CT lesions SUV results

    Objective: To study the effects of lung cancer patients' weight,blood glucose concentration and lesion size of lung cancer on 18F-FDG PET/CT lesions SUV results. Methods: Fifty cases of lung cancer patients without a history of diabetes mellitus were enrolled in this study. Among them, 21 patients with mediastinal metastases were detected. According to clinical routine 18F-FDG PET/CT scanning,automatic extraction of lung cancer SUV, weight and size correction SUV were obtained using the GE Advantage Workstation image processing workstation. Liver reference background SUV was obtained using semiautomatic extraction method of extraction. Lung cancer primary tumors and metastatic lesions diagnosis reference standards were accordant with the liver reference background SUV or SUV shape correction ×1.5+2 × standard deviation. Results: Fifty cases of lung cancer in patients with blood sugar concentration and liver reference background SUV had positive correlation with lung cancer, SUV of primary lung cancer was negatively correlated with blood sugar, but it showed a positive correlation between blood sugar and lung metastases. According to the reference criteria for the diagnosis of 50 primary lung cancer cases and 21 metastatic lung cancer cases before and after the clinical diagnosis, the glucose concentration,lesion size correction accuracies were 90.00%, 71.43% and 100%, 95.24% respectively. Conclusions: Patients' body weight,blood glucose concentration and lesion size significantly affect the accuracy of clinical diagnosis of lung cancer. After correction accuracy, it remarkably improved the clinical diagnosis of lung cancer. The results suggest that when using 18F-FDG PET/CT for lung cancer diagnosis, the effects of body weight, blood glucose concentration and lesion size should be concerned. (authors)

  8. [18F]-2-fluoro-2-deoxyglucose transport kinetics as a function of extracellular glucose concentration in malignant glioma, fibroblast and macrophage cells in vitro

    FDG-PET is used to measure the metabolic rate of glucose. Transport and phosphorylation determine the amount of hexose analog that is phosphorylated and trapped. Competition occurs for both events, such that extracellular glucose concentration affects the FDG image. This study investigated the effect of glucose concentration on the rate of FDG accumulation in three cell lines. The results show that extracellular glucose concentration has a greater impact on the rate of FDG accumulation than the relative abundance of GLUT transporter subtypes

  9. Basal 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    To explore the relationship between basal 18F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent 18F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with 18F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  10. Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

    2015-11-15

    To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  11. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study

    Loft, Annika; Gallamini, Andrea; Hutchings, Martin; Rigacci, Luigi; Specht, Lena; Merli, Francesco; Hansen, Mads; Patti, Caterina; Jakobsen, Annika Loft; Di Raimondo, Francesco; D'Amore, Francesco; Biggi, Alberto; Vitolo, Umberto; Stelitano, Caterina; Sancetta, Rosario; Trentin, Livio; Luminari, Stefano; Iannitto, Emilio; Viviani, Simonetta; Pierri, Ivana; Levis, Alessandro

    2007-01-01

    PURPOSE: Starting from November 2001, 260 newly diagnosed patients with Hodgkin's lymphoma (HL) were consecutively enrolled in parallel Italian and Danish prospective trials to evaluate the prognostic role of an early interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG...... adverse prognostic factors. All but 11 patients were treated with standard ABVD therapy followed by consolidation radiotherapy in case of bulky presentation or residual tumor mass. Conventional radiologic staging was performed at baseline. FDG-PET scan was performed at baseline and after two courses of...

  12. Impact of maximum Standardized Uptake Value (SUVmax) evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) on survival for patients with advanced renal cell carcinoma: a preliminary report

    In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC). A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. FDG uptake was detected in 230 of 243 lesions (94.7%) excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0). The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614). The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012). This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively. The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG-PET/CT. 18F-FDG-PET/CT has potency as an 'imaging biomarker' to provide helpful information for the clinical decision-making

  13. Impact of maximum Standardized Uptake Value (SUVmax evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT on survival for patients with advanced renal cell carcinoma: a preliminary report

    Miura Takeshi

    2010-12-01

    Full Text Available Abstract Background In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT on survival for patients with advanced renal cell carcinoma (RCC. Methods A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. Results FDG uptake was detected in 230 of 243 lesions (94.7% excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0. The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614. The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012. This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively. Conclusions The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG-PET/CT. 18F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making.

  14. Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck

    Ohlsson Tomas

    2009-02-01

    Full Text Available Abstract Background The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24–35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf. The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet, and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion In vitro growth of HNSCC

  15. Procedure guidelines for whole-body 18F-FDG PET and PET/CT in children with malignant diseases

    The purpose of these guidelines is to offer the nuclear medicine and the appropriate interdisciplinary team a framework for performing and reporting positron emission tomography (PET) and the combination with computed tomography (PET/CT) in children with malignant diseases mainly using the radiopharmaceutical 18F-fluorodeoxy-glucose (FDG). These guidelines are based on the recent guidelines of the Paediatric Committee of the European Association of Nuclear Medicine (EANM) (57) and have been translated and adapted to the current conditions in Germany. The adaptation of CT-parameters using PET/CT in children is covered in a more detailed way than in the EANM guideline taking into account that in Germany already a good portion of PET examinations is performed using an integrated PET/CT-scanner. Furthermore, a CT-scan without adaption of the CT acquisition parameters would result in a not tolerably high radiation exposition of the child. There are excellent guidelines for FDG PET and PET/CT in oncology published by the Germany Society of Nuclear Medicine (Deutsche Gesellschaft fuer Nuklearmedizin, DGN) (42) and EANM (4). These guidelines aim at providing additional information on issues particularly relevant to PET and PET/CT imaging in children. These guidelines should be taken in the context of local and national current standards of quality and rules. (orig.)

  16. Regional kinetic constants and cerebral metabolic rate for glucose in normal human volunteers determined by dynamic positron emission tomography of [18F]-2-fluoro-2-deoxy-D-glucose

    Using dynamic [18F]fluorodeoxyglucose (FDG) positron emission tomography with a high-resolution, seven-slice positron camera, the kinetic constants of the original three-compartment model of Sokoloff and co-workers (1977) were determined in 43 distinct topographic brain regions of seven healthy male volunteers aged 28-38 years. Regional averages of the cerebral metabolic rate for glucose (CMRglu) were calculated both from individually fitted rate constants (CMRglukinetic) and from activity maps recorded 30-40 min after FDG injection, employing a four-parameter operational equation with standard rate constants from the literature (CMRgluautoradiographic). Metabolic rates and kinetic constants varied significantly among regions and subjects, but not between hemispheres. k1 ranged between 0.0485 +/- 0.00778 min-1 in the oval center and 0.0990 +/- 0.01347 min-1 in the primary visual cortex. k2 ranged from 0.1198 +/- 0.01533 min-1 in the temporal white matter to 0.1472 +/- 0.01817 min-1 in the cerebellar dentate nucleus. k3 was lowest (0.0386 +/- 0.01482 min-1) in temporal white matter and highest (0.0823 +/- 0.02552 min-1) in the caudate nucleus. Maximum likelihood cluster analysis revealed four homogeneous groups of brain regions according to their respective kinetic constants: (1) white matter and mixed brainstem structures; (2) cerebellar gray matter and hippocampal formations; (3) basal ganglia and frontolateral and primary visual cortex; and (4) other cerebral cortex and thalamus. Across the entire brain, k1 and k2 were positively correlated (r . 0.79); k1 and k3 showed some correlation (r . 0.59); but no significant linear association was found between k2 and k3. A strong correlation with CMRglu could be demonstrated for k1 (r . 0.88) and k3 (r . 0.90), but k2 was loosely correlated (r . 0.56)

  17. Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in gastric carcinoma. Relation to histological subtypes, depth of tumor invasion, and glucose transporter-1 expression

    Variable uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been noticed in positron emission tomography (PET) studies of gastric carcinoma patients, with low uptake occurring especially in some particular histological subtypes and early carcinomas. But this phenomenon has not been adequately explained. The aim of the present study is to clarify FDG uptake in gastric carcinomas especially focusing on histological subtypes, the depth of tumor invasion, and glucose transporter-1 (GLUT-1) expression which is considered to be one of the major factors for higher FDG uptake in human malignant tumors. FDG-PET was performed on 35 preoperative patients with gastric carcinoma. Forty macroscopically distinguishable lesions on a surgical specimen were histologically classified into two subtypes: Cohesive type (papillary adenocarcinoma, tubular adenocarcinoma, and solid type poorly differentiated adenocarcinoma) or Non-cohesive type (signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma). GLUT-1 expression was immunohistochemically determined. Histological parameters (GLUT-1 expression, histological subtypes, the depth of invasion, lymphatic permeation, venous invasion and tumor size) were evaluated, and factors for FDG uptake (detectability and the degree) and GLUT-1 overexpression were determined by multiple regression analysis. Nineteen of 40 gastric carcinomas showed detectable FDG uptake (48%), multiple regression analysis revealed that both the depth of invasion and histological subtypes are independent factors that influence the detectable FDG uptake in gastric carcinoma (R2=0.66). GLUT-1 expression was seen from an early cancer stage and the cohesive type was an independent factor influencing the overexpression of GLUT-1 (R2=0.66). GLUT-1 expression was the most influential factor for the degree of FDG uptake in gastric carcinoma (R2=0.68). This study provided important information on the clinical application of FDG-PET in gastric carcinoma that

  18. Analysis of glucose metabolism in patients with diabetes mellitus by using functional images derived from [sup 18]F-FDG PET

    Ohtake, Tohru; Yokoyama, Ikuo; Watanabe, Toshiaki; Kosaka, Noboru; Momose, Toshimitsu; Nishikawa, Jun-ichi; Serizawa, Takashi; Sasaki, Yasuhito (Tokyo Univ. (Japan). Faculty of Medicine)

    1993-02-01

    Functional images of K complex (KC) and regional myocardial glucose utilization rates (rMGU), derived from F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission computed tomography, were prepared. Using functional images obtained, myocardial glucose metabolism was examined in the fasting state, oral glucose loading (OG), and insulin clamp (IC) condition. The subjects were 10 patients with diabetes mellitus (DM), consisting of 8 with non-insulin dependent DM and 2 with insulin dependent DM, and 4 normal persons. Image quality, derived from both OG and IC approaches, was favorable in the normal group. In the groups of non-insulin dependent DM and insulin dependent DM patients, however, image quality was good with IC method but not with OG method. In the group of non-insulin dependent DM, rMGU derived by IC method was relatively high, but was significantly lower than that in the control group, suggesting a decreased function in glucose transporter. When using OG method, rMGU was even more decreased due to high blood sugar and low insulin. In the group of insulin dependent DM, both IC and OG approaches achieved the same rMGU as that in the control group, with the exception of KC derived by OG method that was decreased due to high blood sugar. In moderate or severe DM, myocardial viability seems to be difficult to evaluate because F-18-FDG uptake is decreased in the ischemic area associated with fasting high blood sugar. Mismatching between blood flow and metabolism is also difficult to detect due to high insulin or glucose load. Thus, myocardial viability should be evaluated in the condition of slightly loaded insulin by decreasing blood sugar. (N.K.).

  19. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    To study the effect of lipid depressing drugs on 18FDG myocardial concentration. The changes of 18FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18FDG). The animals were killed 45 minutes following 18FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  20. Functional imaging of the brain with18F-fluorodeoxyglucose

    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 18F-2-fluoro-2-deoxyglucose ([18F]-FDG) administered as a bolus. [18F]-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 18F activity in the brain determined

  1. {sup 18}F-FDG PET and PET/CT in Burkitt's lymphoma

    Karantanis, Dimitrios, E-mail: dkarantanis@nuclmed.ne [Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN (United States); Durski, Jolanta M.; Lowe, Val J.; Nathan, Mark A.; Mullan, Brian P. [Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN (United States); Georgiou, Evangelos [Medical Physics Department, Medical School, University of Athens (Greece); Johnston, Patrick B. [Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN (United States); Wiseman, Gregory A. [Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN (United States)

    2010-07-15

    Objective: To explore the value of {sup 18}F fluorodeoxy-glucose (FDG) positron emission tomography (PET) in Burkitt's lymphoma. Methods: All Burkitt's lymphoma patients referred for FDG PET or FDG PET/computed tomography (CT) exams at our institution from June 2003 to June 2006 were included. Selected patients were followed and clinical information was reviewed retrospectively. Results from FDG PET-PET/CT, as blindly reviewed by a consensus of two experienced readers, were compared with the status of the disease as determined by other laboratory, clinical and imaging exams and clinical follow-up. FDG PET-PET/CT results were classified as true positive or negative and false positive or negative. The degree of FDG uptake in the positive lesions was semiquantified as maximum standard uptake value (SUVmax). Results: Fifty-seven FDG PET-PET/CT exams were done in 15 patients. Seven exams were done for initial staging, 8 during and 14 after the completion of therapy, and 28 for disease surveillance. For nodal disease FDG PET-PET/CT was true positive in 8, true negative in 47 and false positive in 2 exams (sensitivity 100%, specificity 96%). For extranodal disease FDG PET-PET/CT was true positive in 6, true negative in 48 and false positive in 3 exams (sensitivity 100%, specificity 94%). The mean SUVmax for the positive nodal lesions was 15.7 (range 6.9-21.7, median 18.5) and for extranodal lesions was 14.2 (range 6.2-24.3, median 12.4). Conclusions: FDG PET-PET/CT is sensitive for the detection of viable disease in Burkitt's lymphoma. Affected areas demonstrated high degree of uptake that was reversible upon successful implementation of treatment.

  2. 18F-FDG PET and PET/CT in Burkitt's lymphoma

    Objective: To explore the value of 18F fluorodeoxy-glucose (FDG) positron emission tomography (PET) in Burkitt's lymphoma. Methods: All Burkitt's lymphoma patients referred for FDG PET or FDG PET/computed tomography (CT) exams at our institution from June 2003 to June 2006 were included. Selected patients were followed and clinical information was reviewed retrospectively. Results from FDG PET-PET/CT, as blindly reviewed by a consensus of two experienced readers, were compared with the status of the disease as determined by other laboratory, clinical and imaging exams and clinical follow-up. FDG PET-PET/CT results were classified as true positive or negative and false positive or negative. The degree of FDG uptake in the positive lesions was semiquantified as maximum standard uptake value (SUVmax). Results: Fifty-seven FDG PET-PET/CT exams were done in 15 patients. Seven exams were done for initial staging, 8 during and 14 after the completion of therapy, and 28 for disease surveillance. For nodal disease FDG PET-PET/CT was true positive in 8, true negative in 47 and false positive in 2 exams (sensitivity 100%, specificity 96%). For extranodal disease FDG PET-PET/CT was true positive in 6, true negative in 48 and false positive in 3 exams (sensitivity 100%, specificity 94%). The mean SUVmax for the positive nodal lesions was 15.7 (range 6.9-21.7, median 18.5) and for extranodal lesions was 14.2 (range 6.2-24.3, median 12.4). Conclusions: FDG PET-PET/CT is sensitive for the detection of viable disease in Burkitt's lymphoma. Affected areas demonstrated high degree of uptake that was reversible upon successful implementation of treatment.

  3. [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

    Jensen, Mette Munk; Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram;

    2013-01-01

    Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3'-deoxy-3'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]fluoro-...

  4. The Marinesco-Sjoegren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography

    The Marinesco-Sjoegren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sjoegren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord. The pattern of atrophy resembled that seen in diffuse leukoencephalopathies. Measurements of local cerebral glucose metabolic rates with positron emission tomography revealed no statistically significant differences from normal control subjects in most regions, but metabolic rate was decreased in the thalamus in one patient. The findings support a diffuse white matter disorder in Marinesco-Sjoegren syndrome.Aut

  5. 18-F flourodeoxy glucose positron emission tomography-computed tomography imaging: A viable alternative to three phase bone scan in evaluating diabetic foot complications?

    This paper is based on the initial findings from a prospective ongoing study to evaluate the efficacy of flourodeoxy glucose positron emission tomography-computed tomography (FDG-PET CT) in diabetic foot evaluation. The aim was to compare the diagnostic accuracies of three phase bone scan (TPBS) and FDG PET-CT (FDG-PET) in diabetic foot evaluation. Seventy-nine patients with complicated diabetic foot (osteomyelitis/cellulitis, Charcot's neuropathy) were prospectively investigated. TPBS (15 mci methylene di phosphonate [MDP] intravenous [IV]), followed by FDG-PET (5 mci IV) within 5 days were performed in all patients. Based on referral indication, patients grouped into Group I, n = 36, (?osteomyelitis/cellulitis) and Group II, n = 43 (?Charcot's neuropathy). Interpretation was based on intensity, extent, pattern of MDP and FDG uptake (standardized uptake value) along with CT correlation. Findings were compared with final diagnostic outcome based on bone/soft tissue culture in Group I and clinical, radiological or scintigraphic followup in Group II. Results: Group I: For diagnosing osteomyelitis, TP: TN: FP: FN were 14:5:2:2 by FDG PET and 13:02:05:03 by TPBS respectively. Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of FDG-PET were 87.5%, 71%, 87.5% and 71% and 81.25%, 28.5%, 72% and 40% for TPBS, respectively. Group II: charcot's: cellulitis: Normal were 22:14:7 by FDG PET and 32:5:6 by TPBS, respectively. Flourodeoxy glucose PET-CT has a higher specificity and NPV than TPBS in diagnosing pedal osteomyelitis. TPBS, being highly sensitive is more useful than FDG-PET in detecting Charcot's neuropathy

  6. Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

    Jensen, Mette Munk; Kjaer, Andreas

    2015-01-01

    treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment...... response. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to theapplied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether (18)F-FDG and/or (18)F-FLT PET can...

  7. Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET

    [11C]PIB and [18F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [18F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls. Longitudinal, paired, dynamic [11C]PIB and [18F]FDDNP (90 min each) and static [18F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [11C]PIB and [18F]FDDNP images of binding potential (BPND) and [18F]FDG standardized uptake value ratio (SUVr) images were generated. A significant increase in global cortical [11C]PIB BPND was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [11C]PIB BPND in MCI patients was most prominent in the lateral temporal lobe (p 18F]FDDNP, no changes in global BPND were found. [18F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p 11C]PIB binding (ρ = -0.42, p 18F]FDG uptake (ρ = 0.54, p 18F]FDDNP binding (ρ = -0.18, p = 0.35) were not. [11C]PIB and [18F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [18F]FDDNP seems to be less useful for examining disease progression. (orig.)

  8. Effect of ethanol in BET assay performed by kinetic chromogenic method for (18F) radiopharmaceuticals other than (18F) FDG

    Full text: In recent years, several (18F) labeled radiopharmaceuticals other than 2-(18F)fluoro-2-deoxy-D-glucose have become increasingly important for molecular imaging studies in oncology, and a rapid BET assay is essential to quantify the bacterial endotoxin that may be present in such radiopharmaceutical preparations, prior to use in patients. The radiochemical synthesis of (18F) labelled radiopharmaceuticals like 3'-Deoxy-3'-(18F)fluorothymidine ((18F)FLT), (18F) fluoroazomycinarabinoside ((18F)FAZA) etc is based on use of SEP-PAK cartridge for isolation and purification instead of HPLC purification and requires 15% ethanolic water as elution solvent. BET assay for these radiopharmaceuticals can be routinely performed by Portable Test System (PTS)kinetic reader obtained from Endosafe Inc. The assay is based on kinetic chromogenic method and is known to be inhibited by presence of ethanol. Since all the above mentioned radiopharmaceuticals preparations contains ethanol, the aim of our study was to detect at what ppm/percentage level of ethanol, in final formulation, inhibition in BET assay is observed. The ppm/percentage levels of ethanol in final radiopharmaceutical formulations were detected by gas chromatography. In the present study, the BET Assay for (18F)FDG and (18F)FDG and (18F)FLT was performed at six different dilutions i.e 1:500, 1:200, 1:100, 1:50, 1:20 and 1:10 and all these dilutions were less than the Maximum Valid dilution (MVD). (18F) FDG was chosen as control since the elution solvent for it is 100% water and for all the dilutions mentioned above, the spike recovery was between 50-200%. The CV of negative and positive control samples were found to be 0.0% and less than 10% respectively. However, in case of (18F)FLT, for 1:20 and 1:10 dilutions, the spike recovery was below 50% but coefficient variance of negative and positive control sample were same as (18F)FDG. These results indicate inhibition at 1:20 and 1:10 dilution due to presence of

  9. Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer

    The purpose of this study was to evaluate the impact of [18F]fluorodeoxy-d-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC). FDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients. Results of FDG-PET were compared with those of conventional staging procedures. FDG-PET detected markedly increased FDG uptake in the primary tumours of all 120 patients (sensitivity 100%). Complete agreement between FDG-PET results and other staging procedures was observed in 75 patients. Differences occurred in 45 patients at 65 sites. In 47 sites the FDG-PET results were proven to be correct, and in ten, incorrect. In the remaining eight sites, the discrepancies could not be clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly upstaging ten patients to extensive disease and downstaging three patients by not confirming metastases of the adrenal glands suspected on the basis of CT. Only 1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect brain metastases. In all cases the stage migration led to a significant change in the treatment protocol. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%). The introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures. (orig.)

  10. 123I-Mibg scintigraphy and 18F-Fdg-Pet imaging for diagnosing neuroblastoma

    Bleeker, Gitta; Tytgat, Godelieve Am; Adam, Judit A; Caron, Huib N; Kremer, Leontien Cm; Hooft, Lotty; van Dalen, Elvira C

    2015-01-01

    Background Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood. Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (123I-MIBG), which can be used for imaging the tumour. Moreover, 123I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of 123I-MIBG scintigraphy to detect neuroblastoma varies according to the literature. Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of 123I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of 123I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. Objectives Primary objectives: 1.1 To determine the diagnostic accuracy of 123I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 1.2 To determine the diagnostic accuracy of negative 123I-MIBG scintigraphy in combination with 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. Secondary objectives: 2.1 To determine the diagnostic accuracy of 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 2.2 To compare the diagnostic accuracy of 123I

  11. Alpha clustering in 18F

    We review some of the key experimental and theoretical studies of α-clustering in 18F. Particular attention is given to the 4p-2h nature of such α-clustered states, and the interaction between the holes and clusters is examined in terms of both weak and strongcoupling regimes. The experimental work focuses on α-transfer spectroscopy and α resonant scattering as tools for investigating α-clustering

  12. Procedure guidelines for whole-body {sup 18}F-FDG PET and PET/CT in children with malignant diseases; Empfehlungen zur Durchfuehrung der Ganzkoerper-{sup 18}F-FDG-PET und -PET/CT bei Kindern mit onkologischen Erkrankungen. Anpassung der EANM-Guideline an aktuelle Gegebenheiten in Deutschland

    Franzius, C. [MR-, Nuklearmedizin- und PET/CT-Zentrum Bremen Mitte, Bremen (Germany); Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Stauss, J. [Brigham and Woman' s Hospital, Boston, MA (United States). Dept. of Radiology; Pfluger, T.; Hahn, K. [Ludwig-Maximilians-Univ. Muenchen (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Juergens, K.U. [MR-, Nuklearmedizin- und PET/CT-Zentrum Bremen Mitte, Bremen (Germany); Universitaetsklinikum Muenster (Germany). Inst. fuer Klinische Radiologie; Kluge, R. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Amthauer, H. [Universitaetsklinikum Magdeburg (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Juergens, H. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Kinderheilkunde - Paediatrische Haematologie und Onkologie; Henze, G. [Humboldt Univ. Charite Berlin, Campus Virchow-Klinikum (Germany). Klinik fuer Paediatrie - Onkologie und Haematologie; Stoever, B. [Universitaetsklinikum Charite Berlin, Campus Virchow-Klinikum (Germany). Klinik fuer Strahlenheilkunde

    2010-07-01

    The purpose of these guidelines is to offer the nuclear medicine and the appropriate interdisciplinary team a framework for performing and reporting positron emission tomography (PET) and the combination with computed tomography (PET/CT) in children with malignant diseases mainly using the radiopharmaceutical {sup 18}F-fluorodeoxy-glucose (FDG). These guidelines are based on the recent guidelines of the Paediatric Committee of the European Association of Nuclear Medicine (EANM) (57) and have been translated and adapted to the current conditions in Germany. The adaptation of CT-parameters using PET/CT in children is covered in a more detailed way than in the EANM guideline taking into account that in Germany already a good portion of PET examinations is performed using an integrated PET/CT-scanner. Furthermore, a CT-scan without adaption of the CT acquisition parameters would result in a not tolerably high radiation exposition of the child. There are excellent guidelines for FDG PET and PET/CT in oncology published by the Germany Society of Nuclear Medicine (Deutsche Gesellschaft fuer Nuklearmedizin, DGN) (42) and EANM (4). These guidelines aim at providing additional information on issues particularly relevant to PET and PET/CT imaging in children. These guidelines should be taken in the context of local and national current standards of quality and rules. (orig.)

  13. 18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET), and 18F-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma and radiation necrosis in rats: A PET study

    Introduction: Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG), O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET), and [18F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium (18F-fluoromethylcholine, 18F-FCho) PET in discriminating high-grade tumor from RN. Methods: We developed a glioblastoma (GB) rat model by inoculating F98 GB cells into the right frontal region. Induction of RN was achieved by irradiating the right frontal region with 60 Gy using three arcs with a beam aperture of 3 × 3 mm (n = 3). Dynamic PET imaging with 18F-FDG, 18F-FET, and 18F-FCho, as well as 18F-FDG PET at a delayed time interval (240 min postinjection), was acquired. Results: MRI revealed contrast-enhancing tumors at 15 days after inoculation (n = 4) and contrast-enhancing RN lesions 5–6 months postirradiation (n = 3). On 18F-FDG PET, the mean lesion-to-normal ratio (LNRmean) was significantly higher in GB than in RN (p = 0.034). The difference in the LNRmean between tumors and RN was higher on the late 18F-FDG PET images than on the PET images reconstructed from the last time frame of the dynamic acquisition (this is at a conventional time interval). LNRs obtained from 18F-FCho PET were not significantly different between GB and RN (p = 1.000). On 18F-FET PET, the LNRmean was significantly higher in GB compared to RN (p = 0.034). Conclusions: Unlike 18F-FCho, 18F-FDG and 18F-FET PET were effective in discriminating GB from RN. Interestingly, in the case of 18F-FDG, delayed PET seems particularly useful. Advances in knowledge and implications for patient care: Our results suggest that (delayed) 18F-FDG and 18F-FET PET can be

  14. Estudo do metabolismo da glicose na tuberculose pulmonar ativa utilizando a tomografia por emissão de pósitrons (18F-FDG PET) Evaluation of glucose metabolism in active lung tuberculosis by positron-emission tomography (18F-FDG PET)

    SIDNEY BOMBARDA; JOSÉ SOARES JÚNIOR; MÁRIO TERRA FILHO

    2002-01-01

    Os métodos de imagem utilizados na avaliação da tuberculose pulmonar incluem a radiografia e a tomografia computadorizada do tórax. As imagens obtidas pelos métodos de medicina nuclear permitem estudos funcionais e metabólicos dos órgãos de interesse, através do uso de radiofármacos específicos. Alterações do metabolismo da glicose podem ser detectadas pela tomografia por emissão de pósitrons (PET) utilizando-se o 18F-fluorodesoxiglicose (18F-FDG). Essas alterações estão presentes nas doenças...

  15. [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

    Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) following treatment with belinostat in ovarian cancer in vivo models. In vivo uptake of [18F]FLT and [18F]FDG in human ovary cancer xenografts in mice (A2780) were studied after treatment with belinostat. Mice were divided in 2 groups receiving either belinostat (40 mg/kg ip twice daily Day 0–4 and 6–10) or vehicle. Baseline [18F]FLT or [18F]FDG scans were made before treatment (Day 0) and repeated at Day 3, 6 and 10. Tracer uptake was quantified using small animal PET/CT. Tumors in the belinostat group had volumes that were 462 ± 62% (640 mm3) at Day 10 relative to baseline which was significantly different (P = 0.011) from the control group 769 ± 74% (926 mm3). [18F]FLT SUVmax increased from baseline to Day 10 (+30 ± 9%; P = 0.048) in the control group. No increase was observed in the treatment group. [18F]FDG SUVmean was significantly different in the treatment group compared to the control group (P = 0.0023) at Day 10. Within treatment groups [18F]FDG uptake and to a lesser extent [18F]FLT uptake at Day 3 were significantly correlated with tumor growth at Day 10. [18F]FDG uptake early following treatment initiation predicted tumor sizes at Day 10, suggesting that [18F]FDG may be a valuable biomarker for non-invasive assessment of anti-tumor activity of belinostat

  16. Comparative study of 18F-DOPA, 13 N-ammonia and 18F-FDG PET/CT in primary brain tumors

    To determine the diagnostic reliability of 18F-FDOPA, 13N-ammonia and 18F-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-ammonia and 18F-FDG PET/CT. Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile. Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with 18F-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with 18F-FDG. 18F-FDOPA PET is more reliable than 18F-FDG and 13N-Ammonia PET for evaluating brain tumors. (author)

  17. Comparative Oncology: Evaluation of 2-Deoxy-2-[18F]fluoro-D-glucose (FDG Positron Emission Tomography/Computed Tomography (PET/CT for the Staging of Dogs with Malignant Tumors.

    Stefanie M F Seiler

    Full Text Available 2-Deoxy-2-[18F]fluoro-D-glucose PET/CT is a well-established imaging method for staging, restaging and therapy-control in human medicine. In veterinary medicine, this imaging method could prove to be an attractive and innovative alternative to conventional imaging in order to improve staging and restaging. The aim of this study was both to evaluate the effectiveness of this image-guided method in canine patients with spontaneously occurring cancer as well as to illustrate the dog as a well-suited animal model for comparative oncology.Ten dogs with various malignant tumors were included in the study and underwent a whole body FDG PET/CT. One patient has a second PET-CT 5 months after the first study. Patients were diagnosed with histiocytic sarcoma (n = 1, malignant lymphoma (n = 2, mammary carcinoma (n = 4, sertoli cell tumor (n = 1, gastrointestinal stromal tumor (GIST (n = 1 and lung tumor (n = 1. PET/CT data were analyzed with the help of a 5-point scale in consideration of the patients' medical histories.In seven of the ten dogs, the treatment protocol and prognosis were significantly changed due to the results of FDG PET/CT. In the patients with lymphoma (n = 2 tumor extent could be defined on PET/CT because of increased FDG uptake in multiple lymph nodes. This led to the recommendation for a therapeutic polychemotherapy as a treatment. In one of the dogs with mammary carcinoma (n = 4 and in the patient with the lung tumor (n = 1, surgery was cancelled due to the discovery of multiple metastasis. Consequently no treatment was recommended.FDG PET/CT offers additional information in canine patients with malignant disease with a potential improvement of staging and restaging. The encouraging data of this clinical study highlights the possibility to further improve innovative diagnostic and staging methods with regard to comparative oncology. In the future, performing PET/CT not only for staging but also in therapy control could offer a

  18. 2-deoxy-2-[18F]fluoro-D-mannose positron emission tomography imaging in atherosclerosis.

    Tahara, Nobuhiro; Mukherjee, Jogeshwar; de Haas, Hans J; Petrov, Artiom D; Tawakol, Ahmed; Haider, Nezam; Tahara, Atsuko; Constantinescu, Cristian C; Zhou, Jun; Boersma, Hendrikus H; Imaizumi, Tsutomu; Nakano, Masataka; Finn, Aloke; Fayad, Zahi; Virmani, Renu; Fuster, Valentin; Bosca, Lisardo; Narula, Jagat

    2014-02-01

    Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied (18)F-labeled mannose (2-deoxy-2-[(18)F]fluoro-D-mannose, [(18)F]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [(18)F]FDM and [(18)F]FDG in atherosclerotic lesions in a rabbit model; [(18)F]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[(14)C]carbon-D-glucose ([(14)C]2DG) support at least 35% higher [(18)F]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti-mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation. PMID:24412923

  19. 2-[{sup 18}F]fluoro-2-deoxy-D-glucose positron emission tomography (F.D.G.-PET) can identify chronic lymphocytic leukaemia (C.L.L.) stage A et stage B patients; La tomographie par emission de positons au 2-[{sup 18}F] fluoro-2-desoxy-D-glucose (TEP-FDG) permet d'identifier les stades A et B des leucemies lymphoides chroniques (LLC)

    Berthelot, C.; Vervueren, L.; Le Jeune, J.J.; Couturier, O. [Centre Hospitalier Universitaire, Service de Medecine Nucleaire, 49 - Angers (France); Truchan-Graczyk, M.; Genevieve, F.; Ifrah, N. [Centre Hospitalier Universitaire, Service d' Hematologie, 49 - Angers (France); Poirier, A.L. [BEC, centre Paul-Papin, 49 -Angers (France); Artur-Guillemette, P. [Centre Hospitalier Universitaire, Service de Radiologie, 49 - Angers (France)

    2009-09-15

    Purpose: There is no data in the literature concerning the utility of 2-[{sup 18}F]fluoro-2-deoxy-d-glucose positron emission tomography (F.D.G.-PET) in chronic lymphocytic leukaemia (C.L.L.), except for the diagnosis of Richter's transformations. The purpose of this study was to assess the potential role of F.D.G.-PET in C.L.L. stages A and B. Materials and methods Thirty-five patients (61 {+-} 9 years; 11 women, 24 men; 8 B and 27 A) have benefited of a F.D.G.-PET scan at baseline, for example, before an eventual treatment. F.D.G.-PET scans were analyzed visually and the maximum values of the Standardised Uptake Value (S.U.V.{sub max}) were measured in the main lymph nodes areas. The ability of F.D.G.-PET to differentiate stages A and B patients was evaluated by Student's tests and Receiver Operating Characteristics (R.O.C.) analysis. Results All patients with a normal F.D.G.-PET (n = 18) were stages A. The remaining 17 patients (9 A and 8 B) showed hyper metabolisms in nodal areas above (n = 17) and below (n = 9) the diaphragm, and no visceral involvement. The lymph nodes hyper metabolisms were always bilateral, and of low intensity (= mediastinum; 9 A), or of higher intensity (= liver, 8 B). The S.U.V.{sub max} of stage B (n = 8) were significantly higher than those of the 27 stages A, in all lymph nodes areas except in mediastinum. The highest intensity of F.D.G. uptake was observed in axillary area in stages B patients (S.U.V.max = 2.74 {+-} 1.03). An axillary S.U.V.{sub max} of 1.33 is the most suitable value for the discrimination between stages A and B patients (R.O.C.; AUC = 0.968; sensitivity 1.00; specificity 0.91). Conclusion Lymph nodes hyper metabolisms are constant in the B stage, and more intense than in stage A. These anomalies are always bilateral, unlike what is observed in Richter's transformation. The intensity of axillary lymph nodes F.D.G. uptake can distinguish C.L.L. stages A and B. (authors)

  20. [18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

    Tarkia, Miikka; Saraste, Antti; Stark, Christoffer; Vähäsilta, Tommi; Savunen, Timo; Strandberg, Marjatta; Saunavaara, Virva; Tolvanen, Tuula; Teuho, Jarmo; Teräs, Mika; Metsälä, Olli; Rinne, Petteri; Heinonen, Ilkka; Savisto, Nina; Pietilä, Mikko

    2015-01-01

    Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). Af...

  1. Comparison of 18F-FET and 18F-FDG PET in brain tumors

    The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [18F]-fluorodeoxyglucose (18F-FDG) and O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) in patients with brain lesions suspicious of cerebral gliomas. Methods: Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq 18F-FET, a first PET scan (18F-FET scan) was performed. Thereafter, 240 MBq 18F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection (18F-FET/18F-FDG scan). The cerebral accumulation of 18F-FDG was calculated by decay corrected subtraction of the 18F-FET scan from the 18F-FET/18F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. Results: Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased 18F-FET uptake (>normal brain) in 86% and increased 18F-FDG uptake (>white matter) in 35%. 18F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with 18F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with 18F-FET in 76% and with 18F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with 18F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both techniques. Conclusions: 18F-FET PET is superior to 18F-FDG for biopsy guidance and treatment planning of cerebral gliomas

  2. The radiochemistry of [{sup 18} F]-FDG: the first experience in Mexico; La radioquimica del [{sup 18} F]-FDG: la primera experiencia en Mexico

    Lopez D, F.A. [Unidad PET-Ciclotron, Facultad de Medicina, UNAM, Av. Universidad 3000, Ciudad Universitaria, Coyoacan, 04500 Mexico, D. F. (Mexico)]. e-mail: fred-alonso@correo.unam.mx

    2004-07-01

    The present work describes the more used method for the synthesis of 2 - [{sup 18} F] - fluorine-2-deoxy-D-glucose that is the more used radiopharmaceutical in the nuclear medicine in the cancer diagnostic. The process consists on two chemical reactions: i) [{sup 18} F{sup -}] - nucleophilic radio fluorination and i i) a hydrolysis catalyzed by acid. The first reaction incorporates to the [{sup 18} F]- fluorine labelled inside the organic precursor 1,3,4,6-tetra- O -acetil-2- O-trifluoromethanesulfonyl- {beta}-D-mannopyranose (triflate of mannose). The mechanism of this reaction is a bimolecular nucleophilic substitution (SN{sub 2}) with the ion [{sup 18} F{sup -}] - fluoride; in the second reaction, the hydrolysis of those protective acetyl groups generate the hydroxyl groups free of the [{sup 18} F]-FDG. The process includes an azeotropic distillation and several purification steps. (Author)

  3. Human radiation dosimetry of 6-[{sup 18}F]FDG predicted from preclinical studies

    Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Case Center for Imaging Research, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Chandramouli, Visvanathan; Hatami, Ahmad [Department of Radiology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Huang, Hsuan-Ming; Wu, Chunying [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 and Case Center for Imaging Research, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106 (United States)

    2014-03-15

    Purpose: The authors are developing 6-[{sup 18}F]fluoro-6-deoxy-D-glucose (6-[{sup 18}F]FDG) as an in vivo tracer of glucose transport. While 6-[{sup 18}F]FDG has the same radionuclide half-life as 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (2-[{sup 18}F]FDG) which is ubiquitously used for PET imaging, 6-[{sup 18}F]FDG has special biologic properties and different biodistributions that make it preferable to 2-[{sup 18}F]FDG for assessing glucose transport. In preparation for 6-[{sup 18}F]FDG use in human PET scanning, the authors would like to determine the amount of 6-[{sup 18}F]FDG to inject while maintaining radiation doses in a safe range. Methods: Rats were injected with 6-[{sup 18}F]FDG, euthanized at specified times, and tissues were collected and assayed for activity content. For each tissue sample, the percent of injected dose per gram was calculated and extrapolated to that for humans in order to construct predicted time-courses. Residence times were calculated as areas under the curves and were used as inputs to OLINDA/EXM in order to calculate the radiation doses. Results: Unlike with 2-[{sup 18}F]FDG for which the urinary bladder wall receives the highest absorbed dose due to urinary excretion, with 6-[{sup 18}F]FDG there is little urinary excretion and osteogenic cells and the liver are predicted to receive the highest absorbed doses: 0.027 mGy/MBq (0.100 rad/mCi) and 0.018 mGy/MBq (0.066 rad/mCi), respectively. Also, the effective dose from 6-[{sup 18}F]FDG, i.e., 0.013 mSv/MBq (0.046 rem/mCi), is predicted to be approximately 30% lower than that from 2-[{sup 18}F]FDG. Conclusions: 6-[{sup 18}F]FDG will be safe for use in the PET scanning of humans.

  4. [18F]Fluoride recovery via gaseous [18F]HF

    Mathiessen, Bente; Jensen, Mikael; Zhuravlev, Fedor

    2011-01-01

    Acidification of target water with H2SO4 in a specially constructed glassy carbon/polyethylene apparatus allowed for recovery of up to 82% of [18F]fluoride as [18F]HF gas. The [18F]HF distillate was found to be acid-free but moist; when passed through a solution of tBuPh2SiOTf, it yielded [18F...

  5. CHARACTERIZATION OF THE TANK 18F SAMPLES

    Oji, L.; Click, D.; Diprete, D.

    2009-12-17

    The Savannah River National Laboratory (SRNL) was asked by Liquid Waste Operations to characterize Tank 18F closure samples. Tank 18F slurry samples analyzed included the liquid and solid fractions derived from the 'as-received' slurry materials along with the floor scrape bottom Tank 18F wet solids. These samples were taken from Tank 18F in March 2009 and made available to SRNL in the same month. Because of limited amounts of solids observed in Tank 18F samples, the samples from the north quadrants of the tank were combined into one North Tank 18F Hemisphere sample and similarly the south quadrant samples were combined into one South Tank 18F Hemisphere sample. These samples were delivered to the SRNL shielded cell. The Tank 18F samples were analyzed for radiological, chemical and elemental components. Where analytical methods yielded additional contaminants other than those requested by the customer, these results were also reported. The target detection limits for isotopes analyzed were 1E-04 {micro}Ci/g for most radionuclides and customer desired detection values of 1E-05 {micro}Ci/g for I-129, Pa-231, Np-237, and Ra-226. While many of the minimum detection limits, as specified in the technical task request and task technical and quality assurance plans were met for the species characterized for Tank 18F, some were not met due to spectral interferences. In a number of cases, the relatively high levels of radioactive species of the same element or a chemically similar element precluded the ability to measure some isotopes to low levels. SRNL, in conjunction with the plant customer, reviewed all these cases and determined that the impacts were negligible.

  6. Characterization Of The Tank 18F Samples

    The Savannah River National Laboratory (SRNL) was asked by Liquid Waste Operations to characterize Tank 18F closure samples. Tank 18F slurry samples analyzed included the liquid and solid fractions derived from the 'as-received' slurry materials along with the floor scrape bottom Tank 18F wet solids. These samples were taken from Tank 18F in March 2009 and made available to SRNL in the same month. Because of limited amounts of solids observed in Tank 18F samples, the samples from the north quadrants of the tank were combined into one North Tank 18F Hemisphere sample and similarly the south quadrant samples were combined into one South Tank 18F Hemisphere sample. These samples were delivered to the SRNL shielded cell. The Tank 18F samples were analyzed for radiological, chemical and elemental components. Where analytical methods yielded additional contaminants other than those requested by the customer, these results were also reported. The target detection limits for isotopes analyzed were 1E-04 (micro)Ci/g for most radionuclides and customer desired detection values of 1E-05 (micro)Ci/g for I-129, Pa-231, Np-237, and Ra-226. While many of the minimum detection limits, as specified in the technical task request and task technical and quality assurance plans were met for the species characterized for Tank 18F, some were not met due to spectral interferences. In a number of cases, the relatively high levels of radioactive species of the same element or a chemically similar element precluded the ability to measure some isotopes to low levels. SRNL, in conjunction with the plant customer, reviewed all these cases and determined that the impacts were negligible.

  7. Clinical studies of 18F-FDG and 18F-FP-β-CIT PET imaging in hemi-Parkinson's disease

    Objective: To study the characteristics of 18F-fluorodeoxyglucose (FDG) and 18F-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (18F-FP-β-CIT) PET imaging in patients with hemi-Parkinson's disease (hemi-PD) and to assess their value in early diagnosis. Methods: 34 cases of hemi-PD (Hoehn and Yahr stage I-II) and 16 normal control subjects were selected for this study. 16 patients were performed with 18F-FDG PET imaging, 18 patients with 18F-FP-β-CIF, while 6 patients of them both 18F-FDG and 18F-FP-β-CIT. 30 min after injection of 185-259 MBq 18F-FDG, 3D brain scans were acquired. Region of interest (ROI) analysis and statistical parametric mapping (SPM) were applied. 18F-FP-β-CIT PET imaging was carried out 2-3 h post injection, and (ROI-cerebellum)/cerebellum ratio was calculated. Results: In right hemi-PD, reductions in 18F-FDG metabolism were observed in the left basal ganglia compared with control group, but with no significant difference (P>0.05). The results of SPM analysis showed that a significant reduction in FDG uptake in the left superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and left middle temporal gyrus, whereas a significant increase in the bilateral precentral gyrus , superior parietal lobule, left middle occipital gyrus and left thalamus as compared with the control group. There was a significant reduction in 18F-FP-β-CIT uptake in putamen, its reduction was found not only in the contralateral putamen, but also in the ipsilateral ones, and more pronounced in the contralateral posterior putamen. Conclusions: 18F-FDG PET imaging is non-specific for the early diagnosis of PD. 18F-FP-β-CIT PET imaging could find the changes of striatum dopamine transporter at early stage, therefore it was helpful for early diagnosis and differential diagnosis of PD. Combined with 18F-FDG PET imaging, the changes of local cerebral glucose metabolism in PD could also be evaluated

  8. The radiochemistry of [18 F]-FDG: the first experience in Mexico

    The present work describes the more used method for the synthesis of 2 - [18 F] - fluorine-2-deoxy-D-glucose that is the more used radiopharmaceutical in the nuclear medicine in the cancer diagnostic. The process consists on two chemical reactions: i) [18 F-] - nucleophilic radio fluorination and i i) a hydrolysis catalyzed by acid. The first reaction incorporates to the [18 F]- fluorine labelled inside the organic precursor 1,3,4,6-tetra- O -acetil-2- O-trifluoromethanesulfonyl- β-D-mannopyranose (triflate of mannose). The mechanism of this reaction is a bimolecular nucleophilic substitution (SN2) with the ion [18 F-] - fluoride; in the second reaction, the hydrolysis of those protective acetyl groups generate the hydroxyl groups free of the [18 F]-FDG. The process includes an azeotropic distillation and several purification steps. (Author)

  9. Preliminary investigation of brain 18F-FDG PET imaging in neonate

    Objective: To study brain 18F-fluorodeoxyglucose (FDG) PET imaging and to understand its metabolic function in neonate with pneumonia and premature infants. Methods: Nine neonate with pneumonia and seven premature infants were examined with routine 18F-FDG PET brain scan. Results: The brain 18F-FDG PET image of neonate was significantly different from that of adult and child. The structure of whole brain was not clearly demarcated. The active glucose metabolic areas were in thalamus, cerebellum, sensorimotor cortex and basal ganglia. The 18F-FDG uptake was most in thalamus, while least in cerebral cortex. The image quality showed no significant difference among 1, 2 and 3 min transmission scan for attenuation correction. Conclusions: 18F-FDG PET brain imaging may be one of effective methods to study cerebral function and metabolism in neonate. But the CT transmission time should reduce to be the shortest. (authors)

  10. Recoil 18F-chemistry in fluoroalkanes

    This thesis describes the study of the chemical reactions of recoil 18F-atoms in gaseous fluoromethanes and fluoroethanes. A brief survey of the organic hot atom chemistry is given in Chapter I. Chapter II deals with the experimental procedures used in this investigation. The irradiation facilities, the vapour phase radio-chromatography and the identification, including the synthesis of some fluorocarbons, are described in detail. Chapter III consists of a study on the applicability of perfluoropropene, C3F6, as scavenger for thermal 18F-atoms and radicals. Chapters IV, V, VI and VII deal with 18F-recoil chemistry in gaseous fluoroethanes, using H2S as scavenger. Chapter VIII is a short discussion on the hot 18F-atom based production of 18F-labeled organic compounds via decay of the intermediate 18Ne. A target system is proposed for production of this isotope in high energy and ultra high flux particle beams, which possibly would become available in fast breeders and fusion reactors. (Auth.)

  11. Automated radiosynthesis of [18F]ciprofloxacin

    We transferred the previously published manual synthesis of [18F]ciprofloxacin (decay-corrected RCY: 5.5±1.0%) to an automated synthesis module (TRACERlabTM FXFDG, GE Healthcare) and observed a strong decrease in RCY (0.4±0.4%). When replacing the standard 15-mL glassy carbon reactor of the synthesis module with a 3-mL V-shaped borosilicate glass reactor a considerable improvement in RCY was observed. [18F]Ciprofloxacin was obtained in a RCY of 2.7±1.4% (n=23) with a specific activity at EOS of 1.4±0.5 GBq/µmol in a synthesis time of 160 min. - Highlights: • Automated synthesis of [18F]ciprofloxacin in a TRACERlabTM FXFDG (GE Healthcare) synthesis module was developed. • Dependence of radiochemical yield on reactor type was observed. • 3-mL V-shaped borosilicate glass reactor gave higher radiochemical yield as compared with standard 15-mL glassy carbon reactor. • V-shaped borosilicate glass reactor might also give higher radiochemical yield for other [18F]radiotracers than [18F]ciprofloxacin

  12. Analysis of 18F-FDG PET mapping in malignant tumor patients with depression by SPM

    Objective: To investigate brain 18F-fluorodeoxyglucose (FDG) PET mapping in malignant tumor patients with depressive emotion. Methods: 18F-FDG PET imaging was performed in 21 malignant tumor patients (tumor group) and 21 healthy controls (control group). All were evaluated by self-rating depression scale (SDS)and 24 questions Hamilton rating scale for depression (HAMD). Results: (1) The standard total score of SDS and HAMD of the tumor group were higher than those of the control group (P18F-FDG PET imagings. The abnormalities of glucose metabolism might be related to their depressive emotion. (authors)

  13. 18F-FDG and 18F-FET uptake in experimental soft tissue infection

    The aim of this study was to compare the uptake of 18F-fluoroethyl-L-tyrosine (18F-FET) with that of 18F-fluorodeoxyglucose (18F-FDG) in activated inflammatory white blood cells. Unilateral thigh muscle abscesses were induced in 11 rats by intramuscular inoculation of 0.1 ml of a bacterial suspension (S. aureus, 1.2 x 109 CFU/ml). Four animals were intraperitoneally injected with 130-180 MBq 18F-FDG, four with 140-170 MBq 18F-FET and three with a mixture of 140-170 MBq 18F-FET and 1.8 MBq 14C-deoxyglucose. Autoradiography (10 μm slice thickness) of the abscess and the contralateral muscle was performed and detailed spatial correlation of autoradiography and histopathology (haematoxylin-eosin staining) was obtained. Regions of interest were placed on the abscess wall and the grey values (digitised image intensities) measured were converted to kBq/cc per kBq injected activity per gram (SUV). Areas with increased 18F-FDG uptake corresponded to cellular inflammatory infiltrates mainly consisting of granulocytes. The SUV was calculated to be 4.08±0.65 (mean±SD). The uptake of 18F-FET in activated white blood cells was not increased: the SUV of the abscess wall, at 0.74±0.14, was even below that of contralateral muscle. The low uptake of 18F-FET in non-neoplastic inflammatory cells promises a higher specificity for the detection of tumour cells than is achieved with 18F-FDG, since the immunological host response will not be labelled and inflammation can be excluded. (orig.)

  14. 18F-FDG PET/CT in Neurolymphomatosis: Report of 3 Cases

    Nguyen Xuan Canh; Ngo Van Tan; Tran Thanh Tung; Nguyen Truong Son; Simone Maurea

    2014-01-01

    Neurolymphomatosis is a rare manifestation of non-Hodgkin lymphoma characterized by infiltration of peripheral nerves, nerve roots, plexus and cranial nerves by malignant lymphocytes. This report presents positron emission tomography/computed tomography (PET/CT)imaging with 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) in 3 cases of non-Hodgkin lymphoma with nerve infiltration, including one newly diagnosed lymphoma, one recurrent lymphoma in previous nerve lesions and one newly recurrent lymphoma...

  15. Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose

    The aim of this pilot study was (1) to evaluate the combination of [18F]fluorodeoxyglucose (FDG) and [15O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [15O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: ''large aMMV'' ≥ 10 ml in 40 % of patients and ''small aMMV'' ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. These results suggest that combined PET with FDG and [15O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas. (orig.)

  16. Evaluation of 18F-FDG PET in acute ischemic stroke. Assessment of hyper accumulation around the lesion

    Although pathophysiology of cerebrovascular disease has been reported previously, few clinical studies of glucose metabolism in acute stroke have been published. Purpose of this study is to evaluate glucose metabolism in acute stroke patients by 18F-FDG PET. Twenty-four patients with acute ischemic stroke were involved in this study. All subjects underwent MRI (conventional T1- and T2-weighted images, diffusion-weighted imaging, and MR angiography), CT and 18F-FDG PET. 18F-FDG PET was performed within 1 to 7 days after the first episode. 18F-FDG PET images were visually evaluated as well as MRI and CT images. Four patients out of 24 showed no abnormal 18F-FDG accumulation, while MRI demonstrated abnormal signal area and abnormal vascular findings that suggested acute stroke. Decreased 18F-FDG accumulation corresponding with abnormal signal area on MR images was noted in 20 cases. In 7 cases among these 20 with decreased 18F-FDG, hyper accumulation of 18F-FDG was recognized around the decreased accumulation area. Increased 18F-FDG accumulation (increased glucose metabolization) around the lesion may be due to: acceleration of anaerobic glycolysis, activated repair process of damaged brain tissue, i.e., phagocytosis and gliosis, and neuronal excitation by excito-toxic amino acids which can be released after ischemia. (author)

  17. Longitudinal imaging of Alzheimer pathology using [{sup 11}C]PIB, [{sup 18}F]FDDNP and [{sup 18}F]FDG PET

    Ossenkoppele, Rik; Tolboom, Nelleke; Adriaanse, Sofie F. [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Foster-Dingley, Jessica C.; Boellaard, Ronald; Yaqub, Maqsood; Windhorst, Albert D.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Barkhof, Frederik [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Scheltens, Philip [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands)

    2012-06-15

    [{sup 11}C]PIB and [{sup 18}F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [{sup 18}F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls. Longitudinal, paired, dynamic [{sup 11}C]PIB and [{sup 18}F]FDDNP (90 min each) and static [{sup 18}F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [{sup 11}C]PIB and [{sup 18}F]FDDNP images of binding potential (BP{sub ND}) and [{sup 18}F]FDG standardized uptake value ratio (SUVr) images were generated. A significant increase in global cortical [{sup 11}C]PIB BP{sub ND} was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [{sup 11}C]PIB BP{sub ND} in MCI patients was most prominent in the lateral temporal lobe (p < 0.05). For [{sup 18}F]FDDNP, no changes in global BP{sub ND} were found. [{sup 18}F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p < 0.01). Changes in global [{sup 11}C]PIB binding ({rho} = -0.42, p < 0.05) and posterior cingulate [{sup 18}F]FDG uptake ({rho} = 0.54, p < 0.01) were correlated with changes in Mini-Mental-State Examination score over time across groups, whilst changes in [{sup 18}F]FDDNP binding ({rho} = -0.18, p = 0.35) were not. [{sup 11}C]PIB and [{sup 18}F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [{sup 18}F]FDDNP seems to be less useful for examining disease progression. (orig.)

  18. Influence of 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography on recurrent ovarian cancer diagnosis and on selection of patients for secondary cytoreductive surgery

    Risum, Signe; Høgdall, Claus; Markova, Elena;

    2009-01-01

    The objective of this prospective study was to compare the sensitivities and the specificities of combined 2-(F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT), abdominal/transvaginal ultrasound (US), and CT for diagnosing recurrent ovarian cancer (OC) and to...... 27 (69%) of 39 patients with solitary tumors on US and in 8 (42%) of 19 patients with solitary tumors on CT. We conclude that the diagnostic value of PET/CT for detecting recurrent OC was higher than those of US and CT and that PET/CT more accurately identified patients with solitary recurrence...

  19. Nearly carrier-free 18F-fluorine alkylation and 18F-fluorine acylation

    Preparation and introduction of n.c.a. [18F]-fluoroalkyl and n.c.a. [18F]-fluoroacyl moieties as small prosthetic groups were studied as alternatives to n.c.a. labeling via direct nucleophilic substitution. Starting materials for the n.c.a. [18F]-fluoroalkylation were symmetrical disubstituted alkanes and α-substituted carboxylic acid esters for the n.c.a. [18F]-fluoroacylation. The nucleophilic fluorination of these precursors were systematically investigated with regard to the effect of various important reaction parameters. The monofluorinated prosthetic groups, both monofluorinated alkanes and α-fluorinated carboxylic acid esters, were obtained under optimized conditions with radiochemical yields of about 90% using the efficient fluorination system aminopolyether 2.2.2./potassium carbonate in acetonitrile as solvent. The n.c.a. [18F]-fluoroalkylation of protic functional groups via condensation were performed as a one pot synthesis under basic conditions. The radiochemical yields of these condensation reactions depended on the acid constant of the organic substrates. The highest yields of about 90% of fluoroalkylated products were achieved in acetonitrile with phenols as substrates and n.c.a. [18F]-fluorotosyloxyalkanes as the most valuable fluoroalkylating agents. The n.c.a. [18F]-fluoroacylation of -OH and -NHR functional groups were carried out in two steps. The highest yields of about 85% of fluoroacylated products were obtained in the presence of acids in polar protic solvents when simple primary amines were used as substrates and α-fluoropropionic acid methylester as the best n.c.a. [18F]-fluoroacylating agent. The [18F]-fluoroalkylation via bistosyloxyalkanes was applied to the synthesis of n.c.a. [18F]-fluoroalkylspiperones, potent dopamine receptor ligands to be used for receptor mapping in conjunction with positron emission tomography. (orig.)

  20. In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation

    2-[18F]Fluoro-2-deoxy-D-glucose (18F-FDG) is a widely used PET radiotracer for the in vivo diagnosis of several diseases such as tumours. The positrons emitted by 18F-FDG, travelling into tissues faster than the speed of light in the same medium, are responsible for Cerenkov radiation (CR) emission which is prevalently in the visible range. The purpose of this study is to show that CR escaping from tumour tissues of small living animals injected with 18F-FDG can be detected with optical imaging (OI) techniques using a commercial optical instrument equipped with charge-coupled detectors (CCD). The theory behind the Cerenkov light emission and the source depth measurements using CR is first presented. Mice injected with 18F-FDG or saline solution underwent dynamic OI acquisition and a comparison between images was performed. Multispectral analysis of the radiation was used to estimate the depth of the source of Cerenkov light. Small animal PET images were also acquired in order to compare the 18F-FDG bio-distribution measured using OI and PET scanner. Cerenkov in vivo whole-body images of tumour-bearing mice and the measurements of the emission spectrum (560-660 nm range) are presented. Brain, kidneys and tumour were identified as a source of visible light in the animal body: the tissue time-activity curves reflected the physiological accumulation of 18F-FDG in these organs. The identification is confirmed by the comparison between CR and 18F-FDG images. These results will allow the use of conventional OI devices for the in vivo study of glucose metabolism in cancer and the assessment, for example, of anti-cancer drugs. Moreover, this demonstrates that 18F-FDG can be employed as it is a bimodal tracer for PET and OI techniques. (orig.)

  1. Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake

    Objective: To evaluate whether low carbohydrate diet before 18F-FDG tumor imaging could reduce myocardial 18F-FDG uptake. Methods: From April 2011 to January 2012, 70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases). Patients in control group were on regular diet, while those in test group had low carbohydrate diet in the evening before imaging. Blood samples were taken before injection of 18F-FDG for the measurement of serum glucose, free fatty acid,insulin and ketone body. Whole body 18F-FDG tomography was performed with dual-head coincidence SPECT. The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake, 1 for uptake lower than liver, 2 for uptake similar to liver, 3 for uptake higher than liver, and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated. Two-sample t test, Wilcoxon rank sum test and linear correlation analysis were performed. Results: The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04, respectively (t=-2.75, P<0.05). The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L, t=2.38 and 2.67, both P<0.05. The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group, which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L, t=0.39 and-0.79, both P>0.05). A negative correlation was found between the myocardial uptake of 18F-FDG and serum free fatty acid/ketone body concentration (r=-0.40, -0.33, both P<0.01), respectively. There was no correlation between the myocardial uptake of 18F-FDG and glucose/insulin (r=-0.02, 0.13, both P>0.05), respectively. Conclusion: Low carbohydrate diet

  2. Fluorine-18 radiopharmaceuticals beyond [{sup 18}F]FDG for use in oncology and neurosciences

    Coenen, H.H. [Institut fuer Neurowissenschaften und Medizin, INM-5: Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Elsinga, P.H. [Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Hanzeplein 1, Groningen (Netherlands); Iwata, R. [Cyclotron and Radioisotope Center, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Kilbourn, M.R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, 2276 Medical Science I Building, Ann Arbor, MI 48109 (United States); Pillai, M.R.A., E-mail: m.r.a.pillai@iaea.or [Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Wagramer Strasse 5, A-1400 Vienna (Austria); Rajan, M.G.R. [Radiation Medicine Centre, Bhabha Atomic Research Centre, TMH Annexe, Parel, Mumbai 400012 (India); Wagner, H.N. [School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205-2179 (United States); Zaknun, J.J. [Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Wagramer Strasse 5, A-1400 Vienna (Austria)

    2010-10-15

    Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ({sup 18}F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the {sup 18}F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful {sup 18}F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of {sup 18}F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of {sup 18}F-tracers for oncology and neurosciences. A selection of three groups of {sup 18}F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on 'Development of {sup 18}F radiopharmaceuticals (beyond [{sup 18}F]FDG) for use in oncology and neurosciences' in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more {sup 18}F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

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

    The efficacy of using the 18F-fluoro-deoxyglucose (18F-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 18F-DG technique is capable of providing functional maps in vivo in the human brain

  4. Significance of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of renal cell carcinoma and immunohistochemical glucose transporter 1 (GLUT-1) expression in the cancer

    Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications. Glucose transporter 1 (GLUT-1) is recognized as a major early marker of cellular malignant transformation. The aims of this study were to assess whether FDG-PET is a useful diagnostic tool for renal cell carcinoma and to compare the pathologic characteristics. Nineteen consecutive patients who had renal cell carcinoma were examined using FDG-PET preoperatively. The results of PET were then compared to the histology obtained after radical surgery and the immunoreactivity of GLUT-1 was also studied. Pathologic examination confirmed that all 19 patients suffered from renal cell carcinoma. Increased FDG uptake was found in six of the 19 patients (31.5%). The immmunohistochemical examination of GLUT-1 in renal cell carcinoma produced different results in each patient. There was no correlation with GLUT-1 immunoreactivity and FDG-PET positivity. These results suggest that FDG-PET may not be a useful diagnostic tool for renal cell carcinoma. (author)

  5. Silicon-[18F]Fluorine Radiochemistry: Basics, Applications and Challenges

    Carmen Wängler

    2012-03-01

    Full Text Available Silicon-[18F]fluorine (Si-18F radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-18F and boron-18F based labeling strategies, reshaping the landscape of modern 18F-radiochemistry. All these novel methodologies are driven by the demand for more convenient 18F-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET. The PET methodology requires special radionuclides such as 18F (one of the most prominent examples to be introduced into bioactive molecules. Si-18F radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-18F bond formation, the application of Si-18F tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology.

  6. Clinical Application of 18F-FDG PET in Alzheimer's Disease

    PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. 18F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, 18F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers 18F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of 18F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases

  7. Synthesis of 18F-FDG using improved single-pot acid hydrolysis process

    In order to explore an optimum condition to increase the synthesis yield of 2-18F-2-deoxy-β-D-glucose (18F-FDG) by using improved single-pot acid hydrolysis Chemistry Process Control Unit (CPCU), various production conditions such as the reaction temperature, the time of acid hydrolysis and others were tested. The results showed that the determinant factor which affects the synthesis yield was the quantities of water present in reaction media. The total 18F-FDG synthesis time could be minimized by effective dehydration step and regulating the amount of hydrogen chloride. The synthesis yield could be increased by improving the production conditions of 18F-FDG. (authors)

  8. Paediatric dosimetry of 18F-FDG whole body PET/CT scans

    A combined 18F-FDG (18F-2-deoxy-D-glucose) positron emission tomography/computed tomography (PET/CT) scan provides both the metabolic information from FDG-PET and anatomic information from CT in a single examination. The use of PET/CT for management of malignancies in children has increased over the past few years. This raises an important consideration of radiation exposure in children since they are relatively more radiosensitive than adults and also have a potential for a longer life thereby increasing the probability of manifestation of late radiation effects; particularly cancer. Unfortunately, the data regarding the doses received by children from undergoing such examinations is scarce. The present study aims at estimating the effective doses to paediatric patients from whole body 18F-FDG PET/CT studies. The purpose of the study is to estimate the radiation doses to children from undergoing whole body PET/CT scans using 18F-FDG

  9. Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D-glucosamine

    In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D-glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P 18F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C] glucose and [6-3H]thymidine failed to demonstrate any difference between tumours' metastatic variants in vivo. (Author)

  10. Production of clinical useful quantities of 18 F by an electrostatic tandem accelerator

    The 3 MV electrostatic tandem accelerator in Lund, Sweden, is routinely used for production of the short lived (half-life 110 minutes) isotope 18 F. A beam of 5.7 MeV protons irradiates an open silver-target containing 0.5 ml H218 O water, enriched to 97%. Using a beam current of 10-12 mA and an irradiation time of 60-120 minutes, the nuclear reaction 18 O(p,n)18 F gives a 18 F-yield of typically 2.7-4.5 GBq. The produced 18 F is used for synthesis of 2-18 FDG. This radio pharmaceutical (an analogue to glucose) is used in oncological positron emission tomography (PET) studies at the nearby hospital. In this report technical details of the production, as well as a short outline of the synthesis and application in oncology, are given. (authors)

  11. Clinical Application of {sup 18}F-FDG PET in Alzheimer's Disease

    Ryu, Young Hoon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2008-12-15

    PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. {sup 18}F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, {sup 18}F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers {sup 18}F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of {sup 18}F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases.

  12. Synthesis and evaluation of [[sup 18]F]fluoroprogestins and [[sup 18]F]fluorometoprolol

    De Groot, T.J.

    1993-05-01

    The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and [beta][sub 1]-adrenergic ligands are described. Three approaches towards [[sup 18]F]fluorination are investigated. The first method concerns direct S[sub N]2-substitution, the second approach is the opening of an epoxide, and the third approach is [[sup 18]F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [[sup 18]F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[[sup 18]F]fluorinated progestins is discussed. The synthesis of four 21-[[sup 18]F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6[alpha]-[[sup 18]F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled [beta][sub 1]-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[[sup 18]F]fluorometoprolol, the [[sup 18]F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a [beta][sub 1]-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs.

  13. Automated Synthesis of 18F Analogue of Paclitaxel (PAC): [18F]Paclitaxel (FPAC)

    Kalen, Joseph D.; Hirsch, Jerry I.; Kurdziel, Karen A.; Eckelman, William C; Kiesewetter, Dale O.

    2006-01-01

    A positron-emitting paclitaxel (PAC) derivative could allow in-vivo measurement of multidrug resistance in tumors and, therefore, predict a potential chemotherapeutic benefit to patients. [18F]Paclitaxel was produced using a 2-reaction vessel automated synthesizer followed by HPLC purification. Optimized reaction conditions resulted in radiochemical yields of 21.2 ± 9.6% at end of bombardment, radiochemical purity > 99%, and specific activity of 159 ± 43 GBq/μmol. [18F]Paclitaxel activities o...

  14. Synthesis and evaluation of [18F]fluoroprogestins and [18F]fluorometoprolol

    The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and β1-adrenergic ligands are described. Three approaches towards [18F]fluorination are investigated. The first method concerns direct SN2-substitution, the second approach is the opening of an epoxide, and the third approach is [18F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [18F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[18F]fluorinated progestins is discussed. The synthesis of four 21-[18F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6α-[18F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled β1-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[18F]fluorometoprolol, the [18F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a β1-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs

  15. Reactivity of electrochemically concentrated anhydrous [18F]fluoride for microfluidic radiosynthesis of 18F-labeled compounds

    In order to demonstrate the usefulness of electrochemically concentrated [18F]fluoride the reactivity of the [K+/K.222] 18F− complex concentrated in an aprotic solvent (ca. 60 μL) was evaluated via nucleophilic 18F-substitution reactions through radiosynthesis of [18F]FDG, [18F]FMISO, [18F]flumazenil and [18F]fluoromethyl bromide. The substitutions were carried out in a microfluidic reaction flow cell and the effects of reaction time, temperature, precursor concentration and reaction solvent on the 18F-substitution yields were investigated. The 18F-fluorination yields for the four 18F-labeled compounds under optimized conditions (98% for protected [18F]FDG, 80% for protected [18F]FMISO, 20% for [18F]flumazenil and 60% for [18F]fluoromethyl bromide) were comparable to or higher than those obtained by conventional means. In this study it is clearly demonstrated that electrochemically concentrated [18F]fluoride enables microfluidic radiosynthesis by effectively reducing synthesis times and especially by increasing radiochemical yields of products labile at high temperatures. - Highlights: ► The high reactivity of electrochemically concentrated [18F]fluoride was shown. ► Microfluidic radiosynthesis with the [18F]fluoride effectively reduced synthesis time. Microfluidic radiosynthesis increased yields of products labile at high temperatures.

  16. Development and validation of 2-deoxy-2-chloro-D-glucose impurity analysis in [18F]FDG by three potential-time waveforms of high-performance liquid chromatography/pulsed amperometric detection

    A suitable three potential-time waveforms for the electrochemical detection of 2-deoxy-2-chloro-D-glucose (ClDG) by gold working electrode and palladium reference electrode have been developed and method validation was performed on Waters 2796 Bioalliance HPLC system coupled with pulsed amperometric detection (HPLC/PAD). FDG and ClDG could be completely separated by 50 mM NaOH mobile phase at a flow rate of 1.0 ml/min; 30 deg. C analytical column temperature; and E1 of 200 mV, T1 of 900 mS; E2 of -770 mV, T2 of 10 mS; E3 of 1400 mV, T3 of 10 mS; acquisition delay (AD) of 300 mS. The validation results were shown as follows: (1) in specificity study, mannose, FDG and ClDG could be completely separated and the retention times of these were 6.2, 11.1 and 13.5 min, respectively, with a total run time of 20 min; (2) the intraday repeatable precision expressed with the CV% in six successive analysis was 0.52% (for FDG) and 0.83% (for ClDG); (3) the interday variability precision expressed with the CV% value of the repeatable precision of 3 days was 0.99%, 0.52% and 0.58% for FDG and 0.71%, 0.83% and 1.24% for ClDG; both the CV% of intraday and interday reproducibilities of FDG and ClDG were better than 1.5%; (4) the accuracy and recovery of FDG and ClDG expressed with the percentage of mean value of three successive analysis were 99.75% (for FDG) and 100.68% (for ClDG) which were all greater than 95%; (5) under optimum conditions, the limit of detection of FDG and ClDG was 0.41 and 0.68 μg/ml, and the limit of quantization of FDG and ClDG was 1.24 and 2.04 μg/ml; (6) the correlation coefficient (r) value of linearity is over 0.999 by 5-50 μg/ml ranges of both compounds, respectively; (7) no interference peak effects by composition of mobile phase or increasing/decreasing flow rate or change of temperature was observed

  17. Stereospecific approach to the synthesis of [/sup 18/F]12-deoxy-2-fluoro-D-mannose

    The reaction of methyl 4,6-O-benzylidene-3-O-benzyl-2-O- trifluoromethanesulfonyl-β-D-glucopyranoside in acetonitrile at 750 for 30 min with [/sup 18/F]tetra-n-butylammonium fluoride, followed by silica gel column purification (di-chloromethane: acetone, 95:5) gave the corresponding [/sup 18/F] methyl 4,6-O-benzylidene-3-O-benzyl- 2-fluoro- β -D-mannopyranoside with complete regio- and stereoselectivity (42% radiochemical yield). Hydrolysis of the radiolabeled fluoromannopyranoside intermediate with either 6N HCl or 50% methanesulfonic acid for 30 min at reflux, followed by purification by column chromatography (ion retardation, AG11A8 resin and neutral alumina) gave pure [/sup 18/F]2-deoxy-2-fluoro-D-mannose ([/sup 18/F] 2-FDM) suitable for human injection with a total radiochemical yield (from [/sup 18/F] fluoride ion) of 34%. Since chromatographic identification of 2-fluorodeoxyhexoses does not necessarily constitute a proof of chemical structure, unequivocal evidence of the identity of the final product was obtained using Fourier transform /sup 19/F-NMR. Samples with sufficient fluorine 19 mass when analyzed using /sup 19/F-NMR spectroscopy [Bruker WM-500, 470.56 MHz] after F-18 decay, showed only two peaks corresponding to the two anomers of 2-FDM (α=38.16, β=56.56; D/sub 2/O, solvent; C/sub 6/F/sub 6/, external reference; proton decoupled). The synthetic procedure described here permits the routine preparation of large amounts of [/sup 18/F]/sub 2/-FDM for tomographic studies. In this manner, comparisons of the biological and kinetic behavior of epimerically pure [/sup 18/F]2-deoxy-2-fluoro-D-glucose ([/sup 18/F]2-FDG) and [/sup 18/F]2-FDM in humans are now possible

  18. Diagnostic usefulness of {sup 18}F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma

    Nobusawa, Aiko [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan); Kim, Mai [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Kaira, Kyoichi [Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan); Gunma University Hospital, Oncology Center, Maebashi, Gunma (Japan); Miyashita, Go; Negishi, Akihide; Yokoo, Satoshi [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Oriuchi, Noboru; Higuchi, Tetsuya; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Kanai, Yoshikatsu [Osaka University, Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka (Japan); Oyama, Tetsunari [Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan)

    2013-10-15

    l-[3-{sup 18}F]-{alpha}-Methyltyrosine ({sup 18}F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[{sup 18}F]fluoro-2-deoxy-d-glucose ({sup 18}F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of {sup 18}F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of {sup 18}F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined. The study group comprised 68 OSCC patients who underwent both {sup 18}F-FAMT and {sup 18}F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression. The sensitivity of primary tumour detection by {sup 18}F-FAMT and {sup 18}F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of {sup 18}F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for {sup 18}F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of {sup 18}F-FAMT were significantly higher than those of {sup 18}F-FDG. The uptake of {sup 18}F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis. {sup 18}F-FAMT PET showed higher specificity for detecting malignant lesions than {sup 18}F-FDG PET. The uptake of {sup 18}F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation. (orig.)

  19. Diagnostic usefulness of 18F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma

    l-[3-18F]-α-Methyltyrosine (18F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of 18F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of 18F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined. The study group comprised 68 OSCC patients who underwent both 18F-FAMT and 18F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression. The sensitivity of primary tumour detection by 18F-FAMT and 18F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of 18F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for 18F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of 18F-FAMT were significantly higher than those of 18F-FDG. The uptake of 18F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis. 18F-FAMT PET showed higher specificity for detecting malignant lesions than 18F-FDG PET. The uptake of 18F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation. (orig.)

  20. Pilot Preclinical and Clinical Evaluation of (4S-4-(3-[18F]Fluoropropyl-L-Glutamate (18F-FSPG for PET/CT Imaging of Intracranial Malignancies.

    Erik S Mittra

    Full Text Available (S-4-(3-[18F]Fluoropropyl-L-glutamic acid (18F-FSPG is a novel radiopharmaceutical for Positron Emission Tomography (PET imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years. After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7. 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.ClinicalTrials.gov NCT

  1. Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

    McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2011-10-15

    Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

  2. Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

    Introduction: The aim of the study was to evaluate the uptake of [18F]-1-deoxy-1-fluoro-scyllo-inositol ([18F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [18F]-2-fluoro-2-deoxy-D-glucose ([18F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [18F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [18F]-scyllo-inositol and [18F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [18F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [18F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [18F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [18F]-scyllo-inositol in inflammation was lower than [18F]-FDG. While uptake of [18F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [18F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [18F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [18F]-FDG. The tumour-to-brain ratio of [18F]-scyllo-inositol was also significantly higher than that of [18F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

  3. Comparison of [18F]FDOPA, [18F]FMT and [18F]FECNT for imaging dopaminergic neurotransmission in mice

    Introduction: The clinically established positron emission tomography (PET) tracers 6-[18F]-fluoro-L-DOPA ([18F]FDOPA), 6-[18F]-fluoro-L-m-tyrosine ([18F]FMT) and 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane ([18F]FECNT) serve as markers of presynaptic integrity of dopaminergic nerve terminals in humans. This study describes our efforts to adopt the methodology of human Parkinson's disease (PD) PET studies to mice. Methods: The PET imaging characteristics of [18F]FDOPA, [18F]FMT and [18F]FECNT were analyzed in healthy C57BL/6 mice using the dedicated small-animal PET tomograph quad-HIDAC. Furthermore, [18F]FECNT was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Results: [18F]FDOPA and [18F]FMT failed to clearly visualize the mouse striatum, whereas PET experiments using [18F]FECNT proved that the employed methodology is capable of delineating the striatum in mice with exquisite resolution. Moreover, [18F]FECNT PET imaging of healthy and MPTP-lesioned mice demonstrated that the detection and quantification of striatal degeneration in lesioned mice can be accomplished. Conclusions: This study shows the feasibility of using [18F]FECNT PET to analyze noninvasively the striatal degeneration in the MPTP mouse model of PD. This methodology can be therefore considered as a viable complement to established in vivo microdialysis and postmortem techniques.

  4. Carrier-added and no-carrier-added syntheses of [18F]spiroperidol and [18F]haloperidol

    Syntheses of [18F]haloperidol and [18F]spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added [18F]butyrophenone neuroleptics were prepared in low (18F-neuroleptics were prepared in better (5-17%) yields by 18F-for-19F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described. (author)

  5. [{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 - metabolic considerations

    Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Nics, Lukas [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Ungersboeck, Johanna [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline M. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2010-05-15

    Introduction: Recently, [{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A{sub 3} receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A{sub 3} receptor PET tracers. Methods: In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points (n=3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results: The rate of enzymatic hydrolysis by CES demonstrated Michaelis-Menten constants in a micromolar range (FE-SUPPY, 20.15 {mu}M, and FE-SUPPY:2, 13.11 {mu}M) and limiting velocities of 0.035 and 0.015 {mu}M/min for FE-SUPPY and FE-SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [{sup 18}F]FE-SUPPY was intact compared to 33.1% of [{sup 18}F]FE-SUPPY:2; 30 min pi 30.3% intact [{sup 18}F]FE-SUPPY was found compared to 15.6% [{sup 18}F]FE-SUPPY:2. In brain, [{sup 18}F]FE-SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [{sup 18}F]FE-SUPPY was not observed before 30 min pi Conclusion: Knowing that metabolism in rats is several times faster than in human, we conclude that [{sup 18}F]FE-SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [{sup 18}F]FE-SUPPY.

  6. [18F]FE-SUPPY and [18F]FE-SUPPY:2 - metabolic considerations

    Introduction: Recently, [18F]FE-SUPPY and [18F]FE-SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A3 receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A3 receptor PET tracers. Methods: In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points (n=3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results: The rate of enzymatic hydrolysis by CES demonstrated Michaelis-Menten constants in a micromolar range (FE-SUPPY, 20.15 μM, and FE-SUPPY:2, 13.11 μM) and limiting velocities of 0.035 and 0.015 μM/min for FE-SUPPY and FE-SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [18F]FE-SUPPY was intact compared to 33.1% of [18F]FE-SUPPY:2; 30 min pi 30.3% intact [18F]FE-SUPPY was found compared to 15.6% [18F]FE-SUPPY:2. In brain, [18F]FE-SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [18F]FE-SUPPY was not observed before 30 min pi Conclusion: Knowing that metabolism in rats is several times faster than in human, we conclude that [18F]FE-SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [18F]FE-SUPPY.

  7. Improving the (18)F-fluoromethylcholine ((18)F-FCH) radiochemical yield via optimising the azeotropic drying of non-carrier-added (18)F-fluorine.

    Hassan, Hishar; Abu Bakar, Suharzelim; Halim, Khairul Najah Che A; Idris, Jaleezah; Ahmad Saad, Fathinul Fikri; Nordin, Abdul Jalil

    2015-01-01

    (18)F-Fluoromethylcholine ((18)F-FCH) has been suggested as one of the reputable imaging tracers for diagnosis of prostate tumour in PET/CT examination. Nevertheless, it has never been synthesised in Malaysia. We acknowledged the major problem with (18)F-FCH is due to its relatively low radiochemical yield at the end of synthesis (EOS). Therefore, this technical note presents improved (18)F-FCH radiochemical yields after carrying out optimisation on azeotropic drying of non-carrier-added (18)F-Fluorine. PMID:26395258

  8. A comparison of [/sup 18/F]spiroperidol, [/sup 18/F]benperidol and [/sup 18/F] haloperidol kinetics in baboon brain

    Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-[/sup 18/F]fluorobenzonitrile which was converted to p-[/sup 18/F]fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give [/sup 18/F]spiroperidol ([/sup 18/F]SP), [/sup 18/F]benperidol ([/sup 18/F]BEN), or [/sup 18/F]haloperidol ([/sup 18/F]HAL). Specific activity ranged from 3 to 6 Ci/μmol. Anesthetized baboons were injected with 6-17 mCi of [/sup 18/F]-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; [/sup 18/F]SP was studied to 8 hr. [/sup 18/F]SP and [/sup 18/F]BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. [/sup 18/F]HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (≅0.07% per ml vs. ≅ 0.02% per ml for [/sup 18/F]SP or [/sup 18/F]BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for [/sup 18/F]SP showed > 90% unchanged drug up to 5 min and ≅ 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of [/sup 18/F]SP to the striatum in the four animals studied. Both [/sup 18/F]SP and [/sup 18/F]BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics

  9. [{sup 18}F]FLT is superior to [{sup 18}F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner

    Graf, Nicolas [Technische Universitaet Muenchen, Department of Hematology/Oncology, Munich (Germany); Schoen Klinik Starnberger See, Department of Hematology and Oncology, Berg (Germany); Herrmann, Ken; Numberger, Barbara; Zwisler, Daniela; Wester, Hans-Juergen; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette [Technische Universitaet Muenchen, Institute of Pathology (Helmholtz Zentrum Muenchen), Munich (Germany); Schuster, Tibor [Technische Universitaet Muenchen, Institute of Medical Statistics and Epidemiology, Munich (Germany); Peschel, Christian; Keller, Ulrich; Dechow, Tobias [Technische Universitaet Muenchen, Department of Hematology/Oncology, Munich (Germany); Buck, Andreas K. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Universitaetsklinikum Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany)

    2013-01-15

    Positron emission tomography (PET) with the thymidine analogue [{sup 18}F]fluorothymidine ([{sup 18}F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [{sup 18}F]FLT to the glucose analogue [{sup 18}F]fluorodeoxyglucose ([{sup 18}F]FDG) regarding dose-dependent visualization and prediction of early therapy response. Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [{sup 18}F]FLT and [{sup 18}F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [{sup 18}F]FLT and [{sup 18}F]FDG uptake 48 h later. In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 {mu}g to 200 {mu}g. The mean tumour-to-background ratio (TBR) of [{sup 18}F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [{sup 18}F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [{sup 18}F]FLT uptake, in contrast to a variable and decelerated reduction in [{sup 18}F]FDG uptake. Thus, the increase in [{sup

  10. [18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner

    Positron emission tomography (PET) with the thymidine analogue [18F]fluorothymidine ([18F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [18F]FLT to the glucose analogue [18F]fluorodeoxyglucose ([18F]FDG) regarding dose-dependent visualization and prediction of early therapy response. Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [18F]FLT and [18F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [18F]FLT and [18F]FDG uptake 48 h later. In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 μg to 200 μg. The mean tumour-to-background ratio (TBR) of [18F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [18F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [18F]FLT uptake, in contrast to a variable and decelerated reduction in [18F]FDG uptake. Thus, the increase in [18F]FDG uptake in vivo presumably reflected nonspecific glucose metabolism of

  11. Total synthesis and evaluation of [18F]MHMZ

    Herth, Matthias M; Debus, Fabian; Piel, Markus;

    2008-01-01

    Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall...... radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in...

  12. Anesthesia condition for {sup 18}F-FDG imaging of lung metastasis tumors using small animal PET

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Cheon, Gi Jeong [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)], E-mail: larry@kcch.re.kr; Choi, Chang Woon; Lim, Sang Moo [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)

    2008-01-15

    Small animal positron emission tomography (PET) with {sup 18}F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal {sup 18}F-FDG PET. Methods: To determine the impact of anesthesia on {sup 18}F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of {sup 18}F-FDG in various tissues were evaluated. The {sup 18}F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of {sup 18}F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased {sup 18}F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest {sup 18}F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by {sup 18}F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal {sup 18}F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire {sup 18}F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

  13. Clinical significance of patterns of incidental thyroid uptake at 18F-FDG PET/CT

    Incidental uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological 18F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be “nuisance lesions” by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of 18F-FDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid 18F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave's disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal 18F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy

  14. Compartmental model of 18F-choline

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  15. Monitoring liver tumor therapy with [18F]FDG positron emission tomography

    Positron emission tomography (PET) with [18F]-2-flurodeoxy-glucose (FDG) can be utilized as a functional imaging modality for monitoring liver tumor therapy. We report three cases in which PET-FDG was more useful for this purpose than other imaging methods and tumor markers

  16. Synthesis and quality control of [18F] fluorothymidine

    The Positron Emission Tomography (PET) is a technique that allows early diagnosis of various diseases by detecting metabolic changes of cells, in addition to being a noninvasive technique. The most widely used radiopharmaceutical for PET imaging is [18F] Fludesoxiglucose (18FDG), which is a marker of glucose metabolism and has high sensitivity and specificity for diagnosis and staging of various cancers. However, some carcinomas do not have high glucose consumption, besides 18FDG possess high urinary excretion rate interfering with the detection of tumors in pelvis and high uptake in brain and in inflammation, reducing the contrast tumor / background. The radiotracer 3'-fluoro-L-3'-deoxythymidine (18FLT) is an analogue of thymidine used as an alternative to 18FDG for detecting tumors with high proliferation rate. The aim of this work was to develop [18F] Fluorothymidine synthesis and quality control at the Radiopharmaceuticals Research and Production Facility of CDTN/CNEN. The synthesis was adapted from that used to 18FDG, based on the methodologies described in related papers. Radiochemical purity and impurities levels were determined by HPLC, RTLC and GC techniques. Total synthesis time was 35 minutes and the radiochemical yield in the end of bombardment (EOB) was 7%, with a radiochemical purity of about 93%. Radionuclidic identity and purity, pH, residual solvents, radiochemical and chemical purity were evaluated according to analytical methods described on the literature and on the United States Pharmacopeia (USP 32). Residual levels of Stavudine, Thymine and Thymidine were found and are under toxicological investigation in order to establish a maximum amount allowed in the final product. (author)

  17. Synthesis and quality control of [{sup 18}F] fluorothymidine

    Nascimento, Leonardo Tafas C.; Silva, Juliana B.; Silveira, Marina B.; Santos, Priscilla F.; Faria, Tiago, E-mail: ltcn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The Positron Emission Tomography (PET) is a technique that allows early diagnosis of various diseases by detecting metabolic changes of cells, in addition to being a noninvasive technique. The most widely used radiopharmaceutical for PET imaging is [{sup 18}F] Fludesoxiglucose ({sup 18}FDG), which is a marker of glucose metabolism and has high sensitivity and specificity for diagnosis and staging of various cancers. However, some carcinomas do not have high glucose consumption, besides {sup 18}FDG possess high urinary excretion rate interfering with the detection of tumors in pelvis and high uptake in brain and in inflammation, reducing the contrast tumor / background. The radiotracer 3'-fluoro-L-3'-deoxythymidine ({sup 18}FLT) is an analogue of thymidine used as an alternative to {sup 18}FDG for detecting tumors with high proliferation rate. The aim of this work was to develop [{sup 18}F] Fluorothymidine synthesis and quality control at the Radiopharmaceuticals Research and Production Facility of CDTN/CNEN. The synthesis was adapted from that used to {sup 18}FDG, based on the methodologies described in related papers. Radiochemical purity and impurities levels were determined by HPLC, RTLC and GC techniques. Total synthesis time was 35 minutes and the radiochemical yield in the end of bombardment (EOB) was 7%, with a radiochemical purity of about 93%. Radionuclidic identity and purity, pH, residual solvents, radiochemical and chemical purity were evaluated according to analytical methods described on the literature and on the United States Pharmacopeia (USP 32). Residual levels of Stavudine, Thymine and Thymidine were found and are under toxicological investigation in order to establish a maximum amount allowed in the final product. (author)

  18. Automated synthesis of {sup 18}F analogue of paclitaxel (PAC): [{sup 18}F]Paclitaxel (FPAC)

    Kalen, Joseph D. [Molecular Imaging Center, Department of Radiology, Virginia Commonwealth University, Richmond, VA (United States)]. E-mail: jdkalen@vcu.edu; Hirsch, Jerry I. [Molecular Imaging Center, Department of Radiology, Virginia Commonwealth University, Richmond, VA (United States); Kurdziel, Karen A. [Molecular Imaging Center, Department of Radiology, Virginia Commonwealth University, Richmond, VA (United States); Eckelman, William C. [Molecular Tracer, LLC, Bethesda, MD (United States); Kiesewetter, Dale O. [Positron Emission Tomography Radiochemistry Group, NIBIB, National Institute of Health, Bethesda, MD (United States)

    2007-06-15

    A positron-emitting paclitaxel (PAC) derivative could allow in vivo measurement of multidrug resistance in tumors and, therefore, predict a potential chemotherapeutic benefit to patients. [{sup 18}F]Paclitaxel was produced using a 2-reaction vessel automated synthesizer followed by HPLC purification. Optimized reaction conditions resulted in radiochemical yields of 21.2+/-9.6% at end of bombardment, radiochemical purity >99%, and specific activity of 159+/-43GBq/{mu}mol. [{sup 18}F]Paclitaxel activities of 1.33+/-0.729GBq (n=7) were obtained in sterile, pyrogen-free solution for IV administration.

  19. (18)F-FDG PET imaging of murine atherosclerosis

    Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina;

    2012-01-01

    To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice.......To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

  20. Improved quality control of [18F]FDG by HPLC with UV detection.

    Nakao, Ryuji; Ito, Takehito; Yamaguchi, Masatoshi; Suzuki, Kazutoshi

    2005-11-01

    A conventional high-performance liquid chromatographic (HPLC) method for the analysis of 2-fluoro-2-deoxy-d-glucose (FDG) and 2-deoxy-2-chloro-d-glucose (ClDG) in [18F]FDG preparations is described. This method was based on a postcolumn derivatization with 2-cyanoacetamide (2-CA) and UV detection. FDG and ClDG were separated on a normal-phase column using acetonitrile/water as the mobile phase. The eluate was mixed with 2-CA in sodium borate buffer solution at the outlet of a PTFE coil (10 m x 0.5 mm id) from the column, and the reaction was carried out at 100 degrees C during the passage through the coil. The UV absorbance of the resultant product was monitored at 276 nm. Under optimum conditions, the detection limits [signal-to-noise (S/N) ratio=3] for FDG and ClDG were 0.31 and 0.17 microg/ml for a 20-microl injection volume, respectively, and the linearity ranges were 0.5-100 microg/ml for both compounds. The intra- and interday reproducibilities were better than 2.2% [relative standard deviation (R.S.D.)]. This HPLC separation procedure is also useful for determining the radiochemical purity of [18F]FDG preparations since it allows the analysis of 2-[18F]fluoro-1,3,4,6-tetra-O-acetyl-d-glucose ([18F]TAG), partially hydrolyzed [18F]TAG and [18F]F-. This method can be used at many positron emission tomography (PET) facilities since it does not require an expensive, sophisticated electrochemical detector. PMID:16253817

  1. Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG

    Introduction: The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods: Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [18F]FDG- and [18F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results: Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [18F]FAZA and high-glucose metabolism regions recognized with [18F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy. Conclusions: In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression

  2. Diffuse 18F-FDG Muscle Uptake in Trichinella spiralis Infection.

    Deroose, Christophe M; Van Weehaeghe, Donatienne; Tousseyn, Thomas; Van Rompuy, Anne-Sophie; Vanderschueren, Steven; Blockmans, Daniel; Gheysens, Olivier

    2016-01-01

    Two patients were referred to our emergency department with myalgia, fever, general malaise, eosinophilia, and elevated serum levels of creatine kinase and troponin T. 18F-FDG PET/CT scan was performed showing a diffuse and homogenous moderately elevated glucose uptake in all muscle groups. Trichinella spiralis infection was confirmed by a muscle biopsy and detection of trichinella antibodies. The muscle biopsy was taken in the left quadriceps because of equal involvement of the skeletal muscles. The differential diagnosis of diffuse 18F-FDG muscle uptake should include trichinella infection, in particular, in the presence of infectious symptoms, eosinophilia, and biochemical signs of muscle damage. PMID:26252328

  3. Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides.

    Shi, Hang; Braun, Augustin; Wang, Lu; Liang, Steven H; Vasdev, Neil; Ritter, Tobias

    2016-08-26

    A general method for the synthesis of [(18) F]difluoromethylarenes from [(18) F]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay-corrected) from 10 to 60 %. The (18) F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven (18) F-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [(18) F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design. PMID:27491349

  4. Synthesis and comparison of 4-[18F]F-ADAM, 2-[18F]F-ADAM, N-Desmethyl-4-[18F]F-ADAM and [18F]F-AFM as serotonin transporter imaging agents

    4-[18F]F-ADAM (1a), 2-[18F]F-ADAM (2a), N-Desmethyl-4-[18F]F-ADAM (3a) and [18F]F-AFM (4a ) were synthesized in 1.7, 3.9, 2.9 and 0.6% yield (EOS), respectively, in a synthesis time of ∼120 min from EOB. PET studies in rats showed that the maximum specific uptake ratios of 1a, 2a, 3a and 4a in midbrain were 3.86, 0.73, 0.35 and 2.23, respectively. Thus, in terms of radiochemical yield, specific binding and in vivo stability, 4-[18F]F-ADAM may be the most appropriate SERT imaging agent for human studies. - Highlights: ► Four 18F-labeled radioligands were synthesized and evaluated as SERT imaging agents. ► 4-[18F]F-ADAM and [18F]F-AFM had high specific uptake in SERT-rich brain regions. ► 2-[18F]F-ADAM and N-Desmethyl-4-[18F]F-ADAM had low specific uptake in brain. ► 4-[18F]F-ADAM may be the most appropriate SERT imaging agent for human studies.

  5. [18F]FPEB and [18F]FDEGPECO comparative study of mGlu5 quantification in rodent brain

    The aim of this study is to compare [18F]FPEB and [18F]FDEGPECO for the quantification of mGlu5 receptors in rodent brains. After preparation of radioligands, dynamic PET data was acquired for 90 min. Estimated non-displaceable binding potential (BPND) values were calculated from the non-invasive Logan’s graphical analysis method. Although both radioligands showed similar radiochemical amenability, [18F]FPEB PET showed higher brain uptake and superior binding potential values than those of [18F]FDEGPECO PET (peak brain uptakes in the hippocampus and the striatum: 7.2–8.7 vs. 5.0–6.2, BPND: 7.3–9.6 vs. 0.3–0.4 for [18F]FPEB and [18F]FDEGPECO, respectively). In addition, the target-to-reference ratios for [18F]FPEB is >4 fold than those of [18F]FDEGPECO. From this evidence, we conclude that [18F]FPEB is a superior radioligand for mGlu5 imaging in preclinical studies. - Highlights: • [18F]FPEB and [18F]FDEGPECO had similar radiochemical yields and specific activities. • Although both radioligands have similar initial uptake patterns, the kinetics and behavior at later time phase are different. • Compared with [18F]FDEGPECO PET, [18F]FPEB PET showed remarkably high brain uptake and binding potentials. • [18F]FPEB is a better PET radioligand than [18F]FDEGPECO for imaging mGluR5 in the rodent brains

  6. Evaluating the effect of radiosensitizer early by uptake of 18F-FDG human pancreatic carcinoma cell Patu 8988

    Objective: to evaluate the effect of radiotherapy and joint action with CMNa and 2-DG early by uptake of 18F-FDG in human pancreatic carcinoma cell Patu 8988. Methods: The human pancreatic carcinoma cell Patu 8988 were exposed to a single fraction of X-ray radiation either with glycodidazolum natrium (CMNa) or 2-deoxy-D-glucose (2-DG) or irradiation-only. The uptake of 18F-FDG was calculated 24 and 48 h after irradiation. Results: The differences of 18F-FDG uptake between groups of various dose had no significance 24 h after irradiation (P>0.05). 18F-FDG uptake in the 2-DG groups and CMNa groups were lower than that in the irradiation-only groups (P<0.05 or <0.01). The differences of 18F-FDG uptake in 2-DG groups, CMNa groups and irradiation-only groups had significance 24 and 48 h after irradiation (P<0.05). 18F-FDG uptake decreased with the increasing dose of X-ray. Uptake was positively correlated with the A value 24 and 48 h after irradiation (r=0.759, r=0.814, P<0.01). Conclusion: The uptake of 18F-FDG with human pancreatic carcinoma cell Patu 8988 decreased 24 h after irradiation with 2-DG or CMNa. Response to radiotherapy could be predicted early by 18F-FDG PET scans. (authors)

  7. 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns

    Sanjay Chandrasekaran

    2013-01-01

    Full Text Available Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. 18F-Fluorothymidine (FLT in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT, and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18F-FDG and 18F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67, DNA damage and repair (γH2AX, hypoxia (HIF-1α, and angiogenesis (VEGF. Results. We confirmed that 18F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. 18F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

  8. Effect of subcutaneous injection of insulin on 18F-FDG myocardial imaging in diabetics

    Objective: To evaluate the effect of subcutaneous injection of insulin on 18F-fluorodeoxyglucose (FDG) myocardial imaging in patients with diabetes mellitus. Methods: Fifty-seven patients with coronary artery disease complicated with diabetes mellitus [mean age (60 +- 8) years] underwent 18F-FDG PET and dual isotope simultaneous acquisition SPECT with 99Tcm-MIBI/18F-FDG. Thirty minutes before FDG injection, blood glucose was measured with an automatic glucose analyzer and insulin was subcutaneously used, the dose was adjusted according to the level of blood glucose. Results: Regression analysis showed that the insulin was positively associated with blood glucose. The linear regression analysis showed that the correlation between dose of insulin (y) and blood glucose (x) was good, r 0.8172; the linear regression equation was y = -5.4 + 1.2x. 52 of 57 images were of good quality with 91% success rate. Conclusion: Subcutaneous injection of insulin is an effective and simple method for obtaining cardiac FDG images of good quality in patients with diabetes mellitus

  9. Labeling of complex molecules with 18F, 13N, and 11C

    The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron positron emitters, 11C, 13N and 18F. The goals of the program during the last year were: (1) to complete the modular automated system for important precursor production - formaldehyde, methyliodide, cyanide; (2) to perform animal studies with the 18F-glucose analogues 2FDG and 3FDG and measure the constants for both agents in different animals; and (3) to initiate the development of new fatty acid analogues for the myocardial imaging and metabolism. As part of a collaboration with other groups seeking new agents for myocardium and brain, 9-/sup 123m/Te-telluriumheptadecanoic acid as a myocardial imaging agent was studied. This compound could be used for designing new fatty acid analogues labeled with 11C and 18F that stay in the myocardium because of metabolic inhibition

  10. The use of {sup 18}F-fluoride and {sup 18}F-FDG PET scans to assess fracture healing in a rat femur model

    Hsu, W.K.; Feeley, B.T.; Krenek, L.; Stout, D.B.; Chatziioannou, A.F. [David Geffen School of Medicine at UCLA, Center for Health Sciences, Department of Orthopaedic Surgery, Los Angeles, CA (United States); Lieberman, J.R. [University of Connecticut Health Center, The Musculoskeletal Institute, Department of Orthopaedic Surgery, Farmington, CT (United States)

    2007-08-15

    Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with {sup 18}F-fluoride ion, which localizes in regions of high osteoblastic activity, and {sup 18}F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, {sup 18}F-fluoride, and {sup 18}F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. {sup 18}F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using {sup 18}F-FDG PET imaging at any time point. This study suggests that {sup 18}F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time

  11. 18F-FDG Positron Emission Tomography – An Innovative Technique for the Diagnosis of a Canine Lameness

    Mann, Kelly; Hart, Juliette; Duerr, Felix

    2016-01-01

    Introduction Positron emission tomography (PET) imaging with fluorine-18-fluorodeoxyglucose (18F-FDG) is widely known for its use in the diagnosis and tracking of primary and metastatic tumors via uptake and retention of the radiopharmaceutical by hypermetabolic cells. 18F-FDG is also used to study the normal physiology of glucose uptake, metabolism, and muscle activity during and after exercise. Background A pilot study adding PET imaging to the diagnostic evaluation of canine patients under...

  12. Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?

    Mayerhoefer, Marius E.; Giraudo, Chiara; Senn, Daniela; Hartenbach, Markus; Weber, Michael; Rausch, Ivo; Kiesewetter, Barbara; Herold, Christian J.; Hacker, Marcus; Pones, Matthias; Simonitsch-Klupp, Ingrid; Müllauer, Leonhard; Dolak, Werner; Lukas, Julius; Raderer, Markus

    2016-01-01

    Purpose To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed–time-point 2-18F-fluoro-2-deoxy-d-glucose-positron emission tomography (18F-FDG-PET) performs better than standard–time-point 18F-FDG-PET. Materials and Methods Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic 18F-FDG-PET/computed tomography (CT) and consecutive 18F-FDG-PET/magnetic resonance imaging (MRI), using a single 18F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective 18F-FDG-PET scans at time points 1 (45–60 minutes after tracer injection, TP1) and 2 (100–150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. Results 18F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and 18F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%–84.67%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP1; and 87.0% (CI, 73.26%–100%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and 18F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%–80.9%) for 18F-FDG-PET at TP1, and 76.9% (CI, 54.0%–99.8%) for 18F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). Conclusions Delayed–time-point imaging

  13. 18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

    Persico Marco Giovanni

    2016-06-01

    Full Text Available Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18F-methyl-choline (18F-FCH is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18F-ethyl-tyrosine (18F-FET shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18F-FCH and 18F-FET uptake by human glioblastoma T98G cells.

  14. Pretreatment [18F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [18F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax max ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes

  15. Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

    Striatal dopamine metabolism was studied with 6-[18F]-fluoro-L-dopa (18F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

  16. Ions produced by the positron decay of 18F

    Measurements have been made on the ion species produced by the positron decay. As a positron emitter, 18F was employed. The radionuclide, 18F (tsub(1/2): 110m) was produced by the 16O (3He, p) 18F reaction, using IPCR Cyclotron. The 18F trapped on metal plates were employed as the ion source of a pulse-counting mode of mass spectrometer. The apparatus was the same as previously reported. The ion-expelling voltage was 4.5 - 5.0 kV. The result with the 18F on the copper plate was as follows: m/e 18, 9.5 ; m/e 9, 1.0; m/e 6, 1.4; m/e 4.5, 2.5; m/e 2.8, 4.0. The positron decay of 18F and the inner-shell ionization of 18O formed from 18F may be responsible for this type of spectrum. The yields of the highly charged ions fluctuated with the 18F on the copper plate. However, the fluctuation was not observed with 18F on stainless steel. (auth.)

  17. Imaging malignant melanoma with {sup 18}F-5-FPN

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  18. Novel synthesis and initial preclinical evaluation of 18F-[FDG] labeled rhodamine: a potential PET myocardial perfusion imaging agent

    Myocardial perfusion imaging is one of the most commonly performed investigations in nuclear medicine studies. Due to the clinical importance of [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) and its availability in almost every PET center, a new radiofluorinated [18F]-FDG-rhodamine conjugate was synthesized using [18F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [18F]-FDG-rhodamine conjugate was prepared in quantitative radiochemical yields, with total synthesis time of nearly 20 min and radiochemical purity of greater than 98%, without the need for HPLC purification, which make these approaches amenable for automation. Biodistribution studies in normal rats at 60 min post-injection demonstrated a high uptake in the heart (> 11% ID/g) and favorable pharmacokinetics. Additionally, [18F]-FDG-rhodamine showed an extraction value of 27.63% ± 5.12% in rat hearts. These results demonstrate that [18F]-FDG-rhodamine conjugate may be useful as an imaging agent for the positron emission tomography evaluation of myocardial perfusion. - Highlights: • Division of Nuclear Medicine and Molecular Imaging, Boston Children’s Hospital, Boston • Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston • Harvard Medical School, Boston

  19. Initial evaluation of 18F-NaF, 18F-FDG and cocktail 18F-NaF/18F-FDG PET/CT for evaluation of skeletal metastasis

    Full text: 18F-FDG PET/CT is the commonest radiotracer used for initial staging of malignancy and subsequent treatment strategy evaluation while Sodium 18F PET/CT is a favoured skeletal radiotracer in oncology. The combined administration of 18F and 18F-FDG in a single PET/CT study can be done for cancer detection and initial staging. Materials and Methods: This is a prospective study (July'09-June'10) of 18 patients with histologically proven malignancy, for initial staging (10 carcinoma breast, 2 carcinoma lung, 1 carcinoma prostate, 3 NHL and 2 carcinoma salivary glands) who underwent 18F PET/CT, 18F-FDG PET/CT and combined 18F+18F-FDG PET/CT (cocktail) study on different days for evaluation of malignancy (a total of 3 scans each). There were 7 males and 11 females, age 48 ± 1.4 yrs (range 20-72 yrs). The findings of each study were compared lesion by lesion, with bone marrow aspiration/biopsy/MRI being the reference standard for marrow metastasis and follow up/CT being the reference standard for metastatic lesions. Results: Interpretation of the combined scans (1 lesion missed) compared favourably with that of 18F-FDG PET/CT (2 lesions missed) and 18F PET/CT scan (3 lesions missed). The cocktail and 18F-FDG PET/CT study demonstrated a sensitivity of 93.75% and 87% respectively, but both had equal utility for detection of marrow metastasis. However, the 18F PET/CT study revealed lowest sensitivity 81% but similar specificity i.e. 50% as the cocktail study. 18F-FDG study gave the highest specificity (100%) out of the three. Conclusion: The prospective study demonstrated that a cocktail study using 18F and 18F-FDG is beneficial for cancer detection and initial staging. The combined method opens the feasibility for detection of the visceral, skeletal and marrow metastasis in a single sitting, improving the patient logistic and turnover and with the current CT co-registration, the false positives can be ruled out

  20. BIODISTRIBUTION AND PET IMAGING OF [18F]-FLUOROADENOSINE DERIVATIVES

    Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

    2007-01-01

    Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier we reported radiosynthesis of 2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyl-adenine ([18F]-FAA) and 3′-deoxy-3′-[18F]fluoro-1-β-D-xylofuranosyl-adenine ([18F]FXA). Now we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in six weeks old athymic nude mice (Harlan, Indianapolis, IN) by inoculation of HT-29 cells, wild type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [18F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [18F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [18F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [18F]FAA in spleen and visualization of tumors, and high uptake of [18F]FXA in the heart. Conclusion: These results suggest that [18F]FAA may be useful for tumor imaging, while [18F]FXA may have potential as a heart imaging agent with PET. PMID:17383576

  1. Can 18F-FDG PET improve the evaluation of suspicious breast lesions on MRI?

    Highlights: • Prone 18F-FDG PET can improve the evaluation of suspicious breast lesions on MRI. • 18F-FDG PET's results were better for mass lesions higher than 10 mm. • 18F-FDG PET has the potential to identify more aggressive breast tumors. - Abstract: Objective: To evaluate the impact of adding 18F-fluorine-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the evaluation of suspicious breast lesions on magnetic resonance imaging (MRI). Methods: Sixty patients with suspicious breast lesions on MRI were selected to perform a PET–CT in prone position, dedicated to the evaluation of the breasts. The areas with increased 18F-FDG concentration relative to normal parenchyma were considered positive on PET–CT. Fusion of PET and MRI images (PET–MRI) was performed on a dedicated workstation to better locate corresponding lesions, and its findings were compared with histological results. Results: 76 lesions were evaluated, including 64 mass lesions (84.2%) and 12 non-mass lesions (15.8%). Lesions’ mean diameter on MRI was 29.6 ± 19.2 mm (range 6–94 mm). PET–CT showed increased metabolically activity on 57 lesions (75.0%), with mean maximum SUV of 5.7 ± 5.0 (range 0.8–23.1). On histopathology, there were 17 (22.4%) benign and 59 (79.7%) malignant lesions. Considering all lesions, PET–MRI fusion provided 89.8% sensitivity, 76.5% specificity and 86.8% accuracy. Considering only mass lesions higher than 10 mm, PET–MRI fusion provided 95.8% sensitivity, 83.3% specificity and 93.3% accuracy. Conclusion: The inclusion of 18F-FDG PET on the evaluation of suspicious breast lesions on MRI helped to differentiate benign from malignant breast lesions, especially for mass lesions with a diameter higher than 10 mm

  2. Preparation of 18F labeled octreotide derivatives 18F-Ta-Gluc-TOCA by click chemistry and its biological evaluation

    The preparation of 18F labeled peptides usually need many reaction steps, long time, harsh reaction conditions, which greatly limits the application of 18F labeled PET probe. Using click chemistry for the synthesis of 18F labeled peptides make the reaction conditions more reliable, efficient and selective. The reaction conditions are mild, low cost, and fast. The purpose of this research was to synthesize the glycosylated octreotide derivative quickly and easily, to develop a method of 18F labeled peptides by click chemistry. We also discussed the exploration of the feasibility with 18F labeled glycosylated octreotide derivatives as a somatostatin receptor positive tumor probe. This work prepared 2-18F-azide ethane precursor compounds by nucleophilic substitution and then labeled Pr-Gluc-TOCA by click chemistry, finally we got the product 18F-Ta-Gluc-TOCA by purification. In addition, the in vitro stability and octanol-water partition coefficient of 18F-Ta-Gluc-TOCA were measured. The biodistribution studies of 18F-Ta-Gluc-TOCA in normal mice and tumor bearing nude mice were investigated. The radiochemical purity of 18F-Ta-Gluc-TOCA was 91%. The vitro stability was good. The octanol-water partition coefficient was -0.43± 0.05. The results of biodistribution in normal mice showed rapid clearance from blood, and excreted mainly through the hepatobiliary metabolism, and also through the renal metabolism. The results of the biodistribution in tumor bearing nude mice showed high uptake in the tumor (4.34±0.47% ID/g, 60 min). The finding's suggest that 18F-Ta-Gluc-TOCA is a potential radiotracer for PET imaging of somatostatin receptor positive tumors. (authors)

  3. Automatic extraction analysis of the anatomical functional area for normal brain 18F-FDG PET imaging

    Using self-designed automatic extraction software of brain functional area, the grey scale distribution of 18F-FDG imaging and the relationship between the 18F-FDG accumulation of brain anatomic function area and the 18F-FDG injected dose, the level of glucose, the age, etc., were studied. According to the Talairach coordinate system, after rotation, drift and plastic deformation, the 18F-FDG PET imaging was registered into the Talairach coordinate atlas, and then the average gray value scale ratios between individual brain anatomic functional area and whole brain area was calculated. Further more the statistics of the relationship between the 18F-FDG accumulation of every brain anatomic function area and the 18F-FDG injected dose, the level of glucose and the age were tested by using multiple stepwise regression model. After images' registration, smoothing and extraction, main cerebral cortex of the 18F-FDG PET brain imaging can be successfully localized and extracted, such as frontal lobe, parietal lobe, occipital lobe, temporal lobe, cerebellum, brain ventricle, thalamus and hippocampus. The average ratios to the inner reference of every brain anatomic functional area were 1.01 ± 0.15. By multiple stepwise regression with the exception of thalamus and hippocampus, the grey scale of all the brain functional area was negatively correlated to the ages, but with no correlation to blood sugar and dose in all areas. To the 18F-FDG PET imaging, the brain functional area extraction program could automatically delineate most of the cerebral cortical area, and also successfully reflect the brain blood and metabolic study, but extraction of the more detailed area needs further investigation

  4. 18F-FDG metabolism in a rat model of chronic infarction. A 17-sector semiquantitative analysis

    Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration. (orig.)

  5. [18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

    Miikka Tarkia

    Full Text Available Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days in farm pigs (n = 10. After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33 were harvested for ex vivo measurement of radioactivity and autoradiography (ARG.Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively. Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04. In vivo PET imaging showed the highest target-to-background ratio (TBR of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5 and either intimal thickening (1.2±0.4, P = 1.0 or atheroma (1.6±0.6, P = 0.4.We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.

  6. Synthesis of [18F] FDG under ultrasound promoted without phase transfer catalyst

    2-18F-Fluoro-2-deoxyl-D-glucose(18F-FDG) is one of the most important radiopharma- ceuticals used in PET. Since the synthesis of 18F-FDG in 1978, many methods have been developed. The common method is based on the phase-transfer catalyst(PTS) to promote nucleophilic fluorination. We try to use chemical effects of ultrasound enhance reaction rates to take place of phase transfer catalyst to synthesis of 18F-FDG, and accelerate the ester hydrolysis. A ultrasound bath(20 KHz, 50 w) was used in nucleophilic fluorination and hydrolysis in production of 18F-FDG. The reactor was immersed in center position of ultrasonic bath and the solvent level was under the water bath level by 2 cm, and the temperature of nucleophilic fluorination was 82 degree C. The others were same with classical methods. The yield of 18FFDGOAC4 was measured by radio-TLC. The Rf of free F-18 ion was 0, 18F-FDG was 0.45, 18F-FDG-OAc4 was 0.7. The result showed that the 2-nucleophilic substitution of F ion has relationship with PTS and temperature (Table 1). The ultrasound-promoted nucleophilic substitution reaction have completed 98% at 92 degree C without PTS. The normal nucleophilic reaction have reached 92% at 82 degree C with 10 mg K2.2.2 catalyst. Compared with normal nucleophilic reaction, ultrasound promoted method get lower yield at the same temp, but it can get high fluorination yield at high temp without PTS, and the hangover in reactor was lower 4% nearly. We failed in ultrasonic acceleration of 18F-FDGOAC4 ester hydrolyses with 1 N HCl under room temperature or 90 degree C . Sonochemistry had been used in sonocatalysed nucleophilic reaction and acceleration of ester hydrolyses. We succeed in the synthesis of 18FFDG at substitution reaction. Sonochemistry can been used in other radiopharmaceuticals preparation.

  7. 18F-NaF Positive Bone Metastases of Non 18F-FDG Avid Mucinous Gastric Cancer

    Çiğdem Soydal; Elgin Özkan; Özlem Nuriye Küçük

    2015-01-01

    Detection of gastric cancer bone metastasis is crucial since its presence is an independent prognostic factor. In this case report, we would like to present 18F-NaF positive bone metastases of non 18F-FDG avid gastric mucinous cancer.

  8. Quantification of [18F]-FDG uptake in atherosclerotic plaque. Impact of renal function

    Impaired renal function causes both increased and prolonged tracer availability in the blood-pool which might result in increased tracer accumulation in atherosclerotic lesions. Therefore, the aim of this study was to investigate a possible correlation between the intensity of tracer uptake in atherosclerotic lesions and renal function. Data from 50 [18F]-fluoro-2-deoxy-D-glucose (FDG) scans were visually evaluated for tracer uptake in vessel wall alterations. Lesions were analyzed semiquantitatively by determining the blood-pool standardized uptake values (SUVblood-pools), maximum SUVs (SUVmaxs), and the target-to-background ratio (TBR). These parameters were tested for correlation with estimated glomerular filtration rate (eGFR), and cardiovascular risk factors. Both SUVblood-pools (rs=-0.32, p=0.03) and SUVmaxs for [18F]-FDG (rs=-0.50, p18F]-FDG demonstrated a significant positive correlation with eGFRs (rs=0.21, p=0.02). This study found that both intravascular tracer availability (SUVblood-pool) and intralesional tracer uptake (SUVmax) are influenced by renal function. Calculation of TBR to account for that effect may result in overcorrection in case of [18F]-FDG. Renal insufficiency or subclinical changes in renal function have to be considered as a confounding factor in PET of atherosclerotic lesions. (author)

  9. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.

    Scherer, Daniel J; Psaltis, Peter J

    2016-08-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093

  10. 18F-FDG PET and biomarkers for tumour angiogenesis in early breast cancer

    Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of 18F-FDG to detect angiogenesis in early breast carcinoma using PET/CT. Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1). The SUVmax showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUVmean showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443 18F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, 18F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease. (orig.)

  11. Value of 18F-FDG PET in differentiating Alzheimer's disease with frontotemporal dementia

    Rui-xue CUI

    2014-03-01

    Full Text Available Objective To delineate the pattern of reduction of cerebral glucose metabolism in patients with Alzheimer's disease (AD and frontotemporal dementia (FTD and investigate the value of 18F-FDG PET in the differential diagnosis. Methods Twenty patients with FTD (behavioral variant and 20 AD patients underwent 18F-FDG PET scanning. All the images were compared with that from 20 healthy age-matched control subjects on a voxel-based analysis (VBA using SPM5. Visual analyses of 18F-FDG PET were performed by 2 independent nuclear medicine specialists who were blinded to the clinical background. Results 1 The PET scans of all the patients in 2 groups presented impairment of cortical metabolism. 2 Subjects with AD showed hypometabolism in the bilateral temporoparietal association cortex and posterior cingulate cortex, and hypometabolim in part of bilateral frontal lobes was observed in patients with progression. The metabolic activity was relatively kept in the primary motor-sensor cortex, occipital lobes and subcortical structures (basal ganglia and thalamus. The asymmetric hemispheric hypometabolic involvement was rare and observed in only 2 of 20 cases. 3 Subjects with FTD showed a significant hypometabolism of the frontal lobes and anterior temporal lobes, accompanied by mild to moderate reductions in glucose metabolism in parietal cortices and subcortical structures. The asymmetric hemispheric hypometabolic involvement was commonly observed in 16 of 20 cases with right-dominant type in 4 of 16 cases and left-dominant type in 12 cases. Conclusions 18F-FDG PET is a reliable diagnostic test in distinguishing FTD from AD due to the sharp contrast pattern of cerebral glucose hypometabolism.

  12. Labeling of complex molecules with 18F, 13N, and 11C. Progress report, March 1, 1981-February 28, 1982

    The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron produced positron emitters, 11C, 13N and 18F. The progress report of this year will summarize work done in the last three years. The goals of the program during the last three years were: to build and complete the transport system to Nuclear Medicine; to complete the modular automated system for important precursor production: formaldehyde, methyliodide, cyanide; to perform animal studies with the 18F-glucose analogs 2FDG and 3FDG and measure the rate constants and glucose metabolic rates derived from the Sokoloff model for both agents in different animal species; to initiate the development of new fatty acid analogs for myocardial imaging and metabolism; and to develop syntheses for 18F and 11C sugar analogs

  13. Production And Quality Control Of Radiopharmaceutical 18F-FDG

    18F-FDG is a radiopharmaceutical for imaging diagnosis with PET/CT in Nuclear Medicine. Criteria of injection pharmaceuticals are the highest standards. So, quality assurance and quality control must be followed very strictly. The selection of the procedure for 18F-FDG has based on several criteria: high chemical efficiency, short synthesis time, toxic component free and etc. The quality control of 18F-FDG consist many fields such as: nuclear physic (nuclear purity), radiochemistry (radionuclear purity, radiochemical purity), chemistry (chemical purity), radiation measurement (half life), microbiology (pyrogen, endotoxin), etc. which is following USP, BP or EP. (author)

  14. Comparative study of 18F-FLT PET and 18F-FDG PET of lung cancer

    Xi LIU

    2011-12-01

    Full Text Available Objective The current paper aims to investigate the value of 18F-FLT PET in the diagnosis of lung cancer and the monitoring of tumor proliferation.Methods A total of 36 patients received and cured by the General Hospital of Chinese PLA from September 2005 to October 2008(27 males and 9 females,aged 38 years to 74 years with chest CT suspected lung cancer were examined with 18F-FLT PET.Up to 42 patients(29 males and 13 females,aged 37 years to 75 years received and cured at the same time also underwent 18F-FDG PET.The current experimental results were compared with that of the tumor pathology.Immunohistochemistry was used to measure the expression of cell nuclear antigen of excisional disease tissues Ki-67.Results The 18F-FDG PET standardize uptake value(SUV of lung cancer(SUV,5.2±2.9 was higher than that of the 18F-FLT PET SUV(3.2±1.3(P < 0.05.The sensitivity of 18F-FLT PET for the detection of primary lung cancer was 77%,the specificity was 86%,and the accuracy was 78%.The sensitivity,specificity,and accuracy of 18F-FDG PET were 88%,50%,and 79%,respectively.The sensitivity,specificity,and accuracy for the lymph node staging with 18F-FLT PET were 47%,88% and 75%,respectively,compared with the 68%,84%,and 79% for 18F-FDG PET,respectively.18F-FLT SUV of lung cancer was positively correlated with the Ki-67 index(r=0.8278,P < 0.001 than that of 18F-FDG SUV(r=0.0079,P=0.968.Conclusions 18F-FLT can be made to uptake by specificity of lung cancer tissue,and its uptake value is correlated significantly with the proliferation of lung cancer.Therefore,18F-FLT PET can be applied to assist the diagnosis of lung tumor,and is expected to be a tool to determine the proliferation activity of tumor cells.

  15. Adduct of 2-[18F]FDG and 2-nitroimidazole as a putative radiotracer for the detection of hypoxia with PET: synthesis, in vitro- and in vivo-characterization

    A new sugar-coupled 2-nitroimidazole derivative ([18F]1) has been prepared in good radiochemical yields starting from peracetylated 2-[18F]FDG obtained from an automated 2-[18F]FDG production module. The corresponding glucose derivative 2 has proved to be able to inhibit 2-[18F]FDG uptake into tumor cells in a concentration dependent way. However, [18F]1 failed to show a retention in hypoxic tumor tissue thus excluding itself from further investigations

  16. Differentiating between multiple system atrophy and Parkinson's disease by positron emission tomography with 18F-dopa and 18F-FDG

    Both the striatal 18F-dopa uptake and brain glucose metabolism were studied by PET with 6-L-(18F)fluorodopa (FD) and (18F)fluorodeoxyglucose (FDG) in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson's disease (PD). The FD uptake ratios to the occipital cortex in the MSA patients at 120 min after the administration of FD were 2.07±0.31 and 1.96±0.29 in the caudate and the putamen, respectively, and decreased compared to those in the controls. The same ratios in the PD patients were 2.07±0.36 and 1.74±0.24, respectively, which also decreased, but the decreased uptake in the putamen was more prominent. The caudate-putamen index (CPI) (%). which was calculated by a formula based on the difference in the uptakes in the caudate and putamen divided by the caudate uptake, indicated 5.6±4.6 in the MSA patients and 14.8±5.4 in the PD patients. The CPI for all PD patients was more than 7.0, which was the mean + 2SD for the controls, but the CPI for 3 MSA patients was more than 7.0 (accuracy: 88%). The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal and the temporal cortical glucose metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in the MSA patients decreased significantly in comparison to those in the controls. But, as the glucose metabolic rates in such regions of each patient overlapped in the two groups, the accuracy of the FDG study for differentiation was lower than that of the FD study. The putaminal glucose metabolic rates, for example, in 3 PD patients were less than 6.8 (mg/min/100 ml), which was the mean - 2SD for the controls, while those in 3 MSA patients were more than 6.8 (accuracy: 75%). In addition, the combination of these two methods slightly improved the accuracy. (K.H.)

  17. {sup 18}F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: A clinicopathological study

    Kaira, Kyoichi, E-mail: kkaira1970@yahoo.co.jp [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Abe, Masato [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Takahashi, Toshiaki; Murakami, Haruyasu; Shukuya, Takehito; Kenmotsu, Hirotsugu; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Hayashi, Isamu [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Oriuchi, Noboru [Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Gunma (Japan); Endo, Masahiro [Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Kondo, Haruhiko [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakajima, Takashi [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan)

    2012-09-15

    Background: The usefulness of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of {sup 18}F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of {sup 18}F-FDG PET in primary mediastinal (non-thymic) neoplasms. Methods: Twenty-one patients with mediastinal neoplasms who underwent {sup 18}F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p-mTOR); cell cycle control (p53). Results: Seventeen of 21 patients were imaged on PET system using {sup 18}F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. {sup 18}F-FDG uptake was significantly correlated with Glut1, HIF-1α, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of {sup 18}F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. Conclusion: The amount of {sup 18}F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1α) and upstream components of HIF-1α (EGFR, p-Akt and p-S6K)

  18. 18F FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

    The purpose of this study was to evaluate glucose metabolism of normal human testis on 18F FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. 18F FDG PET/CT was performed in 66 normal healthy men (50.8±13.6 years, range 22-81), and mean standard uptake values (SUV) of 18F FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. 18F FDG PET/CT was also performed in 32 vasectomized men (55.7±7.8 years, range 38-71) and 52 nonvasectomized men (55.4±11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p18F FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular 18F FDG uptake in the normal adult population.

  19. Radiation dosimetry of the translocator protein ligands [18F]PBR111 and [18F]PBR102

    Introduction: The translocator protein (TSPO) ligands [18F]PBR111 and [18F]PBR102 show promise for imaging neuroinflammation. Our aim was to estimate the radiation dose to humans from primate positron emission tomography (PET) studies using these ligands and compare the results with those obtained from studies in rodents. Methods: [18F]PBR111 and [18F]PBR102 PET–computed tomography studies were carried out in baboons. The cumulated activity in the selected source organs was obtained from the volume of interest time–activity curves drawn on coronal PET slices and adjusted for organ mass relative to humans. Radiation dose estimates were calculated in OLINDA/EXM Version 1.1 from baboon studies and compared with those calculated from Sprague–Dawley rat tissue concentration studies, also adjusted for relative organ mass. Results: In baboons, both ligands cleared rapidly from brain, lung, kidney and spleen and more slowly from liver and heart. For [18F]PBR111, the renal excretion fraction was 6.5% and 17% for hepatobiliary excretion; for [18F]PBR102, the renal excretion was 3.0% and 15% for hepatobiliary excretion. The estimated effective dose in humans from baboon data was 0.021 mSv/MBq for each ligand, whilst from rat data, the estimates were 0.029 for [18F]PBR111 and 0.041 mSv/MBq for [18F]PBR102. Conclusion: Biodistribution in a nonhuman primate model is better suited than the rat model for the calculation of dosimetry parameters when translating these ligands from preclinical to human clinical studies. Effective dose calculated from rat data was overestimated compared to nonhuman primate data. The effective dose coefficient for both these TSPO ligands determined from PET studies in baboons is similar to that for [18F]FDG.

  20. 18F-FLT and 18F-FDOPA PET kinetics in recurrent brain tumors

    In this study, kinetic parameters of the cellular proliferation tracer 18F-3'-deoxy-3'-fluoro-l-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis. High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models. Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R2 = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R2 = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R2 = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R2 = 0.25). For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic

  1. Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride

    An improved, automated synthesis of [18F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064±3076 MBq of [18F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both ≥95%. Specific activity was ca. 50 GBq/μmol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [18F]FDOPA.

  2. Silicon-[18F]Fluorine Radiochemistry: Basics, Applications and Challenges

    Carmen Wängler; Alexey Kostikov; Jun Zhu; Joshua Chin; Björn Wängler; Ralf Schirrmacher

    2012-01-01

    Silicon-[18F]Fluorine (Si-18F) radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-F-18 and boron-F-18 based labeling strategies, reshaping the landscape of modern F-18-radiochemistry. All these novel methodologies are driven by the demand for more convenient F-18-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as...

  3. Single-nucleon transfer reactions on 18F

    Simultaneous measurement of the proton-transfer 18F(d, n)19Ne and neutron-transfer 18F(d, p)19F reactions were performed with a 18F radioactive beam at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory. The experiments clarify the nuclear structure of 19Ne near the proton threshold, which is relevant for understanding the rates of proton-induced reactions on 18F in novae. Analogs for several states in the mirror nucleus 19F have not yet been identified in 19Ne, indicating that the level structure of 19Ne in this region is incomplete. We observed 15 levels in 19Ne from the 18F(d, n)19Ne measurement and 18 levels in 19F from the 18F(d, p)19F measurement. Angular distributions were extracted for all strongly populated states and compared to distorted-wave Born approximation calculations. The angular distributions for all the known states in the two nuclei determined in this work are consistent with their previously assigned spins and parities. The spectroscopic factors determined for these levels in the two nuclei are reported.

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

    A model has been designed based on the assumptions of a steady state for glucose consumption, a first-order equilibration of the free 14C-DG pool in the tissue with the plasma level, and relative rates of phosphorylation of 14C-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). 14C is a beta emitter and therefore not suitable for noninvasive imaging in man. With the synthesis of 18F-2-deoxy-2-fluoro-D-glucose (18F-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 14C-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

  5. Combined 18F-Fluoride and 18F-FDG PET/CT Scanning for Evaluation of Malignancy: Results of an International Multicenter Trial

    Iagaru, Andrei; Mittra, Erik; Mosci, Camila; Dick, David W.; Sathekge, Mike; Prakash, Vineet; Iyer, Victor Vishwanath; Lapa, Paula; Isidoro, Jorge; de Lima, Joao M.; Gambhir, Sanjiv Sam

    2012-01-01

    PET/CT examination for evaluation of cancer patients and compared it with separate 18F2 PET/CT and 18F-FDG PET/CT scans. Methods: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating 18F2 PET/CT, 18F-FDG PET/CT, and combined 18F2/18F......-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. Results: 18F2/18FFDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of 18F-FDG PET/CT. In 19 participants, skeletal disease was...... more extensive on 18F2 PET/CT and 18F2/18F-FDG PET/CT than on 18F-FDG PET/CT. In another 29 participants, 18F2 PET/CT and 18F2/18F-FDG PET/CT showed osseous metastases where 18FFDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. Conclusion: This trial...

  6. Radiosynthesis and biodistribution of [18F]-tetracosactide using a semi-automated [18F] SFB production module

    In order to prepare a specific melanocortin type 2 receptor (MC2R) ligand, β1-24-corticotrophin was prepared in one-step reaction with [18F] SFB and β-1-24-corticotrophin pharmaceutical solution (1 mg/mL, pH=6.5). [18F]SFB was prepared in a semi-automated module in two steps with an overall radiochemical yield of 47% to EOB (not-decay corrected) in 90 min. The 18F-labeled intermediates and 18F-labeled peptide was checked by RTLC and HPLC. The results show that the radiochemical purity is >95% and the yield to EOB (not-decay corrected) is 29% for final 18F-labeled peptide at optimized conditions. Preliminary in vivo studies in normal mice were performed to determine biodistribution of the 18F-labeled peptide for 150 min. The results show that the major tracer uptake is consistent with the natural distribution of MC2R receptors in mammals. Testes/blood and testes/muscle ratios for 18F-labeled peptide at 150 min were 184 and 1.56, respectively, and adipocyte/blood and adipocyte/muscle ratios at 120 min were 221 and 142, respectively. The data support the specific receptor binding of the radiolabeled peptide as reported for MC2R receptor accumulation in adipocytes and testes and demonstrates the retention of biological activity of the peptide. This tracer can be used in detection of MC2R distribution in malignancies and sex organ diseases. (authors)

  7. In vivo imaging of monocyte trafficking with 18F-fluorodeoxyglucose labeled monocytes

    Since the ability to monitor in vivo monocyte trafficking would contribute to our understanding of the pathophysiology of various inflammatory disorders, we investigated the feasibility of labeling human monocytes with 18F-FDG. Human monocytes were separated by Ficoll/Hypaque gradient and purity was assessed by flow cytometry. The influence of insulin and/or glucose on labeling efficiency was evaluated. Cell viability and activation was measured with trypan blue exclusion and hydrogen peroxide assays, respectively. Label stability was measured for up to 18 hr, and the effect of insulin pre-incubation on FDG washout was investigated. PET images were acquired in SD rats at various time points after injection of FDG labeled monocytes. Monocytes were >85% pure, and labeling efficiency was 35% for 1x106 cells after 40 min incubation with 2 mCi 18F-FDG without insulin. Pre-incubation with 10∼100 nM insulin significantly increased FDG uptake which reached 400% of baseline levels, whereas presence of glucose or serum decreased FDG uptake. Labeled cells were >90% viable for up to 22 hr, and the labeling process did appear to significantly activate cells, Washout studies however, demonstrated gradual washout of the FDG from monocytes after initial uptake PET images of FDG labeled monocytes in SD rats showed consistent findings. Utilizing insulin effects on cellular glucose metabolism may be a feasible way of labeling monocytes with 18F-FDG for PET imaging. However, gradual washout of FDG after initial uptake poses as a potential problem which needs to be addressed before practical application

  8. A 18F-FDG uptake study of brain and abnormal brain connection in advanced Parkinson's disease

    Objective: To assess the changes in regional glucose metabolism and abnormal brain connection in advanced Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) PET imaging. Methods: Ten advanced PD patients and 10 age-matched healthy subjects underwent 18F-FDG PET imaging at rest-state. Statistical parametric mapping (SPM) was used to investigate regional cerebral metabolic rate of glucose. Results: Compared to age-matched healthy subjects, the regional glucose metabolism increased in bilateral hippocampus, thalamus, precentral cortex (BA6) and lentiform, whereas decreased in bilateral prefrontal motor area (BA46, BA47), parietal area (BA7, BA39) in advanced PD cases. Conclusions: Hypermetabolism in thalamus and lentiform accompany with hypometabolism in prefrontal motor and parietal cortex area was found in advanced PD patients, thereby the abnormal functional connection showed by FDG PET imaging is helpful to the diagnosis and also for the study of the pathophysiology of PD

  9. Mucoepidermoid carcinoma of bronchus in a pediatric patient: {sup 18}F-FDG PET findings

    Lee, Edward Y. [Children' s Hospital Boston and Harvard Medical School, Departments of Radiology and Medicine, Pulmonary Division, Boston, MA (United States); Vargas, Sara O. [Children' s Hospital Boston and Harvard Medical School, Department of Pathology, Boston, MA (United States); Sawicki, Gregory S.; Boyer, Debra [Children' s Hospital Boston and Harvard Medical School, Division of Respiratory Diseases, Boston, MA (United States); Grant, Frederick D.; Voss, Stephan D. [Children' s Hospital Boston and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2007-12-15

    In children, primary neoplasms of the tracheobronchial tree and lungs are rare; most are malignant. Of the primary malignant pulmonary neoplasms arising in childhood, mucoepidermoid carcinoma accounts for approximately 10%. Due to its well-confined local growth within the airway, mucoepidermoid carcinoma commonly produces respiratory symptoms from progressive tracheal or bronchial obstruction. Mucoepidermoid tumor has minimal metastatic potential in children, and local resection alone is the current treatment of choice. Early detection, diagnosis, and surgical resection of mucoepidermoid tumor are especially important in pediatric patients since the bulk of the remaining pulmonary parenchyma can be preserved, thereby decreasing the thoracic deformity and pulmonary functional morbidity. Radiographic and CT imaging findings of bronchial mucoepidermoid carcinoma in children have been described in several case reports. However, to the best of our knowledge, imaging findings of 2-({sup 18}F)-fluoro-2-deoxy-d-glucose positron emission tomography ({sup 18}F-FDG PET) of mucoepidermoid carcinoma of the bronchus in pediatric patients have not been well established. We report a mucoepidermoid carcinoma arising from the right upper lobe bronchus in a 15-year-old girl with an emphasis on the {sup 18}F-FDG PET findings. (orig.)

  10. Mucoepidermoid carcinoma of bronchus in a pediatric patient: 18F-FDG PET findings

    In children, primary neoplasms of the tracheobronchial tree and lungs are rare; most are malignant. Of the primary malignant pulmonary neoplasms arising in childhood, mucoepidermoid carcinoma accounts for approximately 10%. Due to its well-confined local growth within the airway, mucoepidermoid carcinoma commonly produces respiratory symptoms from progressive tracheal or bronchial obstruction. Mucoepidermoid tumor has minimal metastatic potential in children, and local resection alone is the current treatment of choice. Early detection, diagnosis, and surgical resection of mucoepidermoid tumor are especially important in pediatric patients since the bulk of the remaining pulmonary parenchyma can be preserved, thereby decreasing the thoracic deformity and pulmonary functional morbidity. Radiographic and CT imaging findings of bronchial mucoepidermoid carcinoma in children have been described in several case reports. However, to the best of our knowledge, imaging findings of 2-(18F)-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) of mucoepidermoid carcinoma of the bronchus in pediatric patients have not been well established. We report a mucoepidermoid carcinoma arising from the right upper lobe bronchus in a 15-year-old girl with an emphasis on the 18F-FDG PET findings. (orig.)

  11. {sup 18}F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis..; La TEP au {sup 18}F-FDG dans la pathologie inflammatoire et infectieuse: intestinale, prothetique, fibrose, sarcoidose, tuberculose..

    Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C. [Hospital Universitari de Bellvitge, Service TEP-Centre IDI, Services de Medecine Interne, Barcelone (Spain)

    2008-10-15

    Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, {sup 68}Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ({sup 18}F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. {sup 18}F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). {sup 18}F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. {sup 18}F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of {sup 18}F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection.

  12. Complementary roles of tumour specific PET tracer 18F-FAMT to 18F-FDG PET/CT for the assessment of bone metastasis

    The usefulness of 18F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [18F]-3-fluoro-alpha-methyl tyrosine (18F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of 18F-FAMT PET/CT to complement 18F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both 18F-FDG and 18F-FAMT PET/CT within 1 month of each other. 18F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the 18F-FAMT in the corresponding lesions were evaluated. A total of 72 18F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. 18F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P 18F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher 18F-FAMT uptake than those of adenocarcinoma. No significant difference in 18F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of 18F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that 18F-FAMT uptake was confirmed by 18F-FDG uptake suggests that 18F-FAMT PET/CT has the potential to complement 18F-FDG PET/CT for the detection of bone metastases. (orig.)

  13. Usefulness of 18F-FDG PET in intrahepatic cholangiocarcinoma

    Surgical resection is the only curative treatment strategy for intrahepatic cholangiocarcinoma (CC). Therefore, accurate staging is essential for appropriate management of patients with CC. We assessed the usefulness of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the staging of CC. We undertook a retrospective review of FDG PET images in 21 patients (10 female, 11 male; mean age 57 years) diagnosed with CC. Ten patients had hilar CC and 11, peripheral CC. Patients underwent abdominal magnetic resonance imaging (MRI) (n=20) and computed tomography (CT) (n=12) for the evaluation of primary tumours, and chest radiography and whole-body bone scintigraphy for work-up of distant metastases. For semi-quantitative analysis, the maximum voxel standardised uptake value (SUVmax) was obtained from the primary tumour. All peripheral CCs showed intensely increased FDG uptake, and some demonstrated ring-shaped uptake corresponding to peripheral rim enhancement on CT and/or MRI. In nine of the ten patients, hilar CCs demonstrated increased FDG uptake of a focal nodular or linear branching appearance. The remaining case was false negative on FDG PET. One patient with a false negative result on MRI demonstrated increased uptake on FDG PET. Among the ten hilar CCs, FDG uptake was intense in only two patients and was slightly higher than that of the hepatic parenchyma in the remaining patients. For the detection of lymph node metastasis, FDG PET and CT/MRI were concordant in 16 patients, and discordant in five (FDG PET was positive in three, and CT and MRI in two). FDG PET identified unsuspected distant metastases in four of the 21 patients; all of these patients had peripheral CC. FDG PET is useful in detecting the primary lesion in both hilar and peripheral CC and is of value in discovering unsuspected distant metastases in patients with peripheral CC. FDG PET could be useful in cases of suspected hilar CC with non-confirmatory biopsy and radiological

  14. Toxoplasmic Lymphadenitis Mimicking a Metastatic Thyroid Carcinoma at {sup 18}F-FDG-PET/CT

    Treglia, Giorgio; Bongiovanni, Massimo; Ceriani, Luca; Paone, Gaetano; Giovanella, Luca [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

    2013-12-15

    A 28-year-old woman underwent total thyroidectomy for a papillary thyroid carcinoma in the right thyroid lobe (pTx, pN1b). Subsequently a {sup 131}I-ablation (4.4 GBq) was performed. Four years later the patient presented increased thyroglobulin (Tg) serum levels (8.4 μg/l) during thyroxine treatment. Furthermore, enlarged hypoechoic and round-shaped bilateral cervical lymph nodes were detected at cervical ultrasonography (US). Based on laboratory and US findings suspicious for lymph nodal recurrence of thyroid carcinoma, the patient underwent an {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) to check for distant metastases (Fig. 1). The patient underwent a US-guided fine-needle aspiration cytology on an {sup 18}F-FDG-avid cervical lymph-node. The smears were hypercellulated and consisted of numerous small- to medium-sized lymphocytes, macrophages, dendritic cells and tingible body macrophages. The cytological diagnosis was consistent with that of reactive lymphadenitis. Serological test revealed elevated IgM and IgG anti-Toxoplasma antibodies with a very low IgG-avidity, indicating an acute toxoplasmosis. Serum Tg was then measured by using heterophilic antibody blocking tubes, as previously reported, and serum value dropped to <0.2 μg/l. It is well known that antibody interference may falsely increase serum Tg; in particular, increased anti-Toxoplasma antibodies likely interfered to the Tg measurement in our case. Additionally, activated granulocytes and macrophages may display significantly increased glucose consumption, giving false-positive results at {sup 18}F-FDG-PET/CT in oncological patients. Few reports have described toxoplasmic infection mimicking malignancy at {sup 18}F-FDG-PET/CT; these findings were found mainly in immunodepressive patients or with history of lymphoma. Conversely, we described here a case of toxoplasmosis inducing false-positive Tg measurement, neck US and {sup 18}F

  15. 18F-FDG-PET-CT imaging findings of recurrent intracranial haemangiopericytoma with distant metastases

    Chan, W S W; Zhang, J; Khong, P. L.

    2010-01-01

    A 42-year-old woman presented with local recurrence and distant lung and liver metastases 7 years after resection of a primary intracranial haemangiopericytoma. Whole-body 18F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET)-CT scan showed no increased uptake in local recurrence or distant metastases except for a focus of increased FDG uptake within a hepatic metastasis. The hypermetabolic area correlated with an intratumoral hypoenhancing area on the CT scan. PET-CT scan may...

  16. Evaluation of mild hypothermia therapy for neonatal hypoxic-ischaemic encephalopathy on brain energy metabolism using 18F-fluorodeoxyglucose positron emission computed tomography

    Luo, Mei; Li, Qingping; DONG, WENBIN; Zhai, Xuesong; Kang, Lan

    2014-01-01

    It remains unclear whether mild hypothermia affects energy metabolism in the brain tissue of newborns with hypoxic-ischaemic encephalopathy (HIE). The current study aimed to investigate the effect of mild hypothermia on energy metabolism in neonatal HIE and assess brain energy metabolism using position emission tomography/computed tomography (PET/CT) scanning. The mean standardised uptake values of 18F-fluorodeoxyglucose (18F-FDG) were used to determine the glucose metabolic rate in various b...

  17. [18F]FDG PET/CT outperforms [18F]FDG PET/MRI in differentiated thyroid cancer

    To evaluate the diagnostic potential of PET/MRI with [18F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [18F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [18F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [18F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [18F]FDG PET/MRI was inferior to low-dose [18F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [18F]FDG PET/MRI was equal to contrast-enhanced neck [18F]FDG PET/CT. Therefore, [18F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast agent is contraindicated. (orig.)

  18. Imaging of lung metastasis tumor mouse model using [{sup 18}F]FDG small animal PET and CT

    Kim, June Youp; Woo, Sang Keun; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)] (and others)

    2007-02-15

    The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [{sup 18}F]FDG small animal PET and clinical CT. The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 .deg. C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [{sup 18}F]FDG and compared pattern of [{sup 18}F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [{sup 18}F]FDG image was obtained and fused with anatomical clinical CT image. Average blood glucose concentration in normal mice were 128.0 {+-} 22.87 and 86.0 {+-} 21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6 {+-} 0.48 and 12.1 {+-}0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [{sup 18}F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [{sup 18}F]FDG small animal PET image was confirmed by fusion image using clinical CT. Tumor imaging in small animal lung region with [{sup 18}F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [{sup 18}F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

  19. Study of wear analysis with {sup 18}F

    Schmidt, N.; Nolen, J.A.; Blumenthal, D.J. [and others

    1995-08-01

    We are studying the possible use of low-energy radioactive beams for the wear analysis of various industrial components (e.g. engine parts and materials for orthopedic implants). Previous experiments with {sup 7}Be and {sup 22}Na studied components at implantation depths of several tens of micrometer. In a first series of experiments we implanted {sup 18}F ions into the surface layer, which opens the possibility to study wear in the critical first micrometer of various materials. {sup 18}F was produced via the p({sup 18}O, {sup 18}F)n reaction at E{sub 18}{sub O} = 110 MeV using a 1.22-mg/cm{sub 2} polypropylene foil as a hydrogen target. The {sup 18}F{sup 9+} ions were separated at {theta}=0{degrees} from the incident {sup 18}O{sup 8+} beam with the split-pole spectrograph. In order to allow for a rapid change of irradiation samples, the {sup 18}F ions penetrated a thin HAVAR foil and were implanted into the sample which was located outside the vacuum chamber behind the pressure window. The depth distribution of the {sup 18}F was tested by implantation into a series of 1.5-{mu} thick Mylar foils which were subsequently measured with respect to their {sup 18}F activity using a Si-surface barrier detector. The localization of the {sup 18}F ions was found to be better than 1.5 {mu}. The implantation depth could be varied in the range between 1.5 {mu} - 9 {mu} by choosing the appropriate distance between pressure window and implantation sample. The wear rate was determined by measuring the (decay-corrected) decrease of the activity remaining in the sample after it was polished with Emery paper. In a first experiment the wear of stainless steel could be measured by this technique with a sensitivity of better than 100 nm. A paper describing these results is under preparation.

  20. PET of Malignant Melanoma Using 18F-Labeled Metallopeptides

    Ren, Gang; Liu, Zhe; Miao, Zheng; Liu, Hongguang; Subbarayan, Murugesan; Chin, Frederick T.; Zhang, Lan; Sanjiv S Gambhir; CHENG Zhen

    2009-01-01

    Melanocortin type 1 receptor (MC1R), also known as α-melanocyte–stimulating hormone (α-MSH) receptor, is an attractive molecular target for melanoma imaging and therapy. An 18F-labeled linear α-MSH peptide (18F-FB-Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 [NAPamide]) shows promising melanoma imaging properties but with only moderate tumor uptake and retention. A transition metal rhenium-cyclized α-MSH peptide, ReO[Cys3,4,10,D-Phe7,Arg11] α-MSH3–13 (ReCCMSH(Arg11)), has shown high in vitro bind...

  1. [18F]haloperidol binding in baboon brain in vivo

    The binding of [18F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [18F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET

  2. Dynamic {sup 18}F-FDG PET for Assessment of Tumor Physiology in Two Breast Carcinoma Xenografts

    Kristian, Alexandr; Nilsen, Line B.; Roe, Kathrine; Revheim, Monaelisabeth; Engebraten, Olav; Maelandsmo, Gunhild M.; Holm, Ruth; Malinen Eirik; Seierstad, Therese [Oslo Univ. Hospital, Oslo (Norway)

    2013-09-15

    To compare dynamic 2-deoxy-2-[{sup 18}F]fluoro-D-glucose positron emission tomography ({sup 18}F-FDG PET) parameters in two selected human breast cancer xenografts and to evaluate associations with immunohistochemistry and histology. Dynamic {sup 18}F-FDG PET of luminal-like MAS98.06 and basal-like MAS98.12 xenografts was performed, and the compartmental transfer rates (k{sub 1}, k{sub 2}, k{sub 3}), blood volume fraction (v{sub B}) and metabolic rate of {sup 18}F-FDG(MR{sub FDG}) were estimated from pharmacokinetic model analysis. After sacrifice, analyses of hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose transport receptor (GLUT1) and necrosis (HE) was performed. The level of hexokinase 2 (HK2) was estimated from Western blot analysis. The {sup 18}F-FDG uptake curves for the two xenografts were significantly different (p<0.05). k{sub 1} and v{sub B} were higher for MAS98.12 (p<0.01), while k{sub 3} was higher for MAS98.06 (p<0.01). MAS98.12 had a higher fraction of stromal tissue and higher microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06 MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In both models significant correlations were found between k{sub 1} and the GLUT1 score, between k{sub 3} and the level of HK2, and between v{sub B} and MVD. Significant differences in dynamic {sup 18}F-FDG parameters between the two human breast cancer xenografts were found. The differences could be explained by underlying histological and physiological characteristics.

  3. {sup 18F} FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

    Moon, Seung Hwan; Eo, Jae Sun; Lee, Jong Jin; Chung, June Key; Lee, Dong Soo; Lee, Myung Chul [Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2011-12-15

    The purpose of this study was to evaluate glucose metabolism of normal human testis on {sup 18F} FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. {sup 18F} FDG PET/CT was performed in 66 normal healthy men (50.8{+-}13.6 years, range 22-81), and mean standard uptake values (SUV) of {sup 18F} FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. {sup 18F} FDG PET/CT was also performed in 32 vasectomized men (55.7{+-}7.8 years, range 38-71) and 52 nonvasectomized men (55.4{+-}11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p<0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r=-0.427, p=0.0003; r=0.435, p=0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p<0.0378 and p=0.0001, respectively). Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular {sup 18F} FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular {sup 18F} FDG uptake in the normal adult population.

  4. Experimental study of the molecular mechanisms of myocardial ischemic memory with 18F-FDG PET/CT imaging

    This study was aimed to explore whether the changes of mRNA and the existence and duration of ischemic 18F-FDG uptake correlate with the extent of myocardial ischemia in ischemia-reperfusion canine model. The 20-minute (n= 4) and 40-minute (n=4) coronary artery occlusion followed by 24 h of open-artery reperfusion in canine model were per- formed. All dogs underwent fasting (>12 h) dynamic 18F-FDG PET/CT and 99Tcm-MIBI SPECT imaging at baseline, 1 h and 24 h after reperfusion. When all imaging were completed, myocardial samples from the ischemic and nonischemic region were obtained, and the mRNA expression of glucose transporter-l (GLUT-1), glucose transporter-4 (GLUT-4), and heart-fatty acid binding protein (H-FABP) were estimated by Real Time PCR. There was no difference in the ratio of hypoperfused region/nomoperfused region of 18F-FDG up- take between the 20-minute group and 40-minute group at baseline. When examined at 1 h, increased 18F-FDG uptake was observed in the 40-minute group. When estimated at 24 h, only the 40-minute group showed slightly higher 18F-FDG uptake than baseline, whereas no such difference was demonstrated in the 20-minute group. Similar mRNA expression of GLUT-1, GLUT-4 and H-FABP were demonstrated in the nonischemic regions between the 2 groups, whereas increased expressions of GLUT-1 and GLUT-4, and decreased H-FABP mRNA were demonstrated in the ischemic regions. The changes of mRNA expression were more obvious in the 40 minute group than in the 20-minute group. The results showed that the existence and persistent period of ischemic 18F-FDG uptake (ischemic memory) was correlated with the extent of myocardial ischemia. (authors)

  5. Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET

    Idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are the most common movement disorders associated with neurodegenerative disease. A clinical differential diagnosis of IPD and atypical Parkinsonian disorders, such as MSA and PSP, is often complicated by the presence of symptoms common to both groups. Since Parkinsonism has a different pathophysiology in the cortical and subcortical brain structures, assessing the regional cerebral glucose metabolism may assist in making a differential diagnosis of Parkinsonism. The 18F-FDG PET images of IPD, MSA and PSP were assessed using statistical parametric mapping (SPM) in order to determine the useful metabolic patterns. Twenty-four patients with Parkinsonism: eight patients (mean age 67.9±10.7 years; M/F: 3/5) with IPD, nine patients (57.9±9.2 years; M/F: 4/5) with MSA and seven patients (67.6±4.8 years; M/F: 3/4) with PSP were enrolled in this study. All patients with Parkinsonism and 22 age-matched normal controls underwent 18F-FDG PET, (after 370 MBq 18F-FDG). The three groups and the individual IPD, MSA and PSP patients were compared with a normal control group using a two-sided t-test of SPM (uncorrected P100 voxel). The IPD, MSA and PSP groups showed significant hypometabolism in the cerebral neocortex compared to the normal control group. The MSA group showed significant hypometabolism in the putamen, pons and cerebellum compared to the normal controls and IPD groups. In addition, PSP showed significant hypometabolism in the caudate nucleus, the thalamus, midbrain and the cingulate gyrus compared to the normal controls, the IPD and the MSA groups. In conclusion, an assessment of the 18F-FDG PET images using SPM may be a useful adjunct to a clinical examination when making a differential diagnosis of Parkinsonism

  6. Analysis of 18F-FDG PET images of patients with sarcoidosis

    Objective: To analyse 18F-fluorodeoxyglucose (FDG) PET images of patients with sarcoidosis, make an abstract of image characteristics. Methods: Twenty-four cases with sarcoidosis underwent both PET and CT. Among them, 5 were with pathologic evidence and had clinical symptoms, 19 were with positive Kveim test but asymptomatic. All 24 cases kept a fast of 6 h and the blood glucose was controlled below 6.7 mmol/L before injection of FDG. 40 min after administration, PET scan was performed with Siemens ECAT 47. After getting images through reconstruction by computer, the location and contour of the lesions were reviewed; the sizes and standardized uptake value (SUV) were measured. Results: For all 24 cases, strings of nodules were observed along the hili of lungs and the mediastinum, one of them had a nodule with high uptake of 18F-FDG in the left axilla in addition to the nodules along the hili of lungs and mediastinum. Sizes of nodules of 5 cases with symptoms and of 19 without symptoms were (2.16±0.67) and (1.55±0.21) cm, respectively; SUV were 2.68 ± 0.58 and 1.46±0.24, respectively. There was significant difference in the sizes and SUV of nodules between 5 with symptoms and 19 without symptoms (P 18F-FDG PET image characteristics of sarcoidosis i. e. strings of nodules distributing along the lung hili and mediastinum. Sizes of nodules were bigger and uptakes of 18F-FDG were higher for cases with symptoms than those for the asymptomatic cases

  7. Different metabolic patterns analysis of Parkinsonism on the {sup 18}F-FDG PET

    Juh, Rahyeong; Kim, Jaesung; Moon, Daehyuk; Choe, Boyoung; Suh, Tasuk E-mail: suhsanta@catholic.ac.kr

    2004-09-01

    Idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are the most common movement disorders associated with neurodegenerative disease. A clinical differential diagnosis of IPD and atypical Parkinsonian disorders, such as MSA and PSP, is often complicated by the presence of symptoms common to both groups. Since Parkinsonism has a different pathophysiology in the cortical and subcortical brain structures, assessing the regional cerebral glucose metabolism may assist in making a differential diagnosis of Parkinsonism. The {sup 18}F-FDG PET images of IPD, MSA and PSP were assessed using statistical parametric mapping (SPM) in order to determine the useful metabolic patterns. Twenty-four patients with Parkinsonism: eight patients (mean age 67.9{+-}10.7 years; M/F: 3/5) with IPD, nine patients (57.9{+-}9.2 years; M/F: 4/5) with MSA and seven patients (67.6{+-}4.8 years; M/F: 3/4) with PSP were enrolled in this study. All patients with Parkinsonism and 22 age-matched normal controls underwent {sup 18}F-FDG PET, (after 370 MBq {sup 18}F-FDG). The three groups and the individual IPD, MSA and PSP patients were compared with a normal control group using a two-sided t-test of SPM (uncorrected P<0.01, extent threshold >100 voxel). The IPD, MSA and PSP groups showed significant hypometabolism in the cerebral neocortex compared to the normal control group. The MSA group showed significant hypometabolism in the putamen, pons and cerebellum compared to the normal controls and IPD groups. In addition, PSP showed significant hypometabolism in the caudate nucleus, the thalamus, midbrain and the cingulate gyrus compared to the normal controls, the IPD and the MSA groups. In conclusion, an assessment of the {sup 18}F-FDG PET images using SPM may be a useful adjunct to a clinical examination when making a differential diagnosis of Parkinsonism.

  8. 18F FDG PET/CT in differential diagnosis of Parkinsonian disorders

    Full text: Differential diagnosis of Parkinsonian disorders can be challenging in the early phase of disease course. Positron Emission Tomography (PET) imaging with 18F Fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of glucose metabolism in patients with idiopathic Parkinson's Disease (PD) as well as variant forms of Parkinsonism such as Multisystem Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and cortico basal ganglionic degeneration (CBGD). In this study we assessed the utility of 18F FDG PET/CT in the differential diagnosis Parkinsonian syndromes. 66 Parkinsonian patients with a mean age of 59.6 ± 11.50 years, male: female ratio of 3.12:1, age range of 35-84 years with a disease duration of 2.6 ± .68 years were referred for FDG PET to determine whether their scan patterns could distinguish idiopathic Parkinsons from the Parkinson plus syndromes. Approximately 60 minutes following intravenous injection of 370 MBq of 18F-FDG, PET/CT scan of the brain was acquired in a whole-body Full Ring PET/CT scanner (Discovery STE16 camera). A low dose CT was obtained on the same area without IV contrast for attenuation correction and coregistration. Images were reconstructed using a 3D VUE algorithm and slices were reformatted into transaxial, coronal and sagittal views. Subsequently the images were processed and visually analyzed on Xeleris workstation. Images were classified by visual analysis into the various subgroups, those with normal to increased basal ganglia uptake were classified into Idiopathic Parkinson's (40/45) and when basal ganglia uptake was decreased they were Parkinsons Plus (19/21). The study demonstrates that 18F FDG PET performed at the time of initial referral for parkinsonism could accurately classify patients into Parkinson's disease and Parkinson plus subtypes

  9. Conversion of arterial input functions for dual pharmacokinetic modeling using Gd-DTPA/MRI and 18F-FDG/PET.

    Poulin, Eric; Lebel, Réjean; Croteau, Etienne; Blanchette, Marie; Tremblay, Luc; Lecomte, Roger; Bentourkia, M'hamed; Lepage, Martin

    2013-03-01

    Reaching the full potential of magnetic resonance imaging (MRI)-positron emission tomography (PET) dual modality systems requires new methodologies in quantitative image analyses. In this study, methods are proposed to convert an arterial input function (AIF) derived from gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) in MRI, into a (18)F-fluorodeoxyglucose ((18)F-FDG) AIF in PET, and vice versa. The AIFs from both modalities were obtained from manual blood sampling in a F98-Fisher glioblastoma rat model. They were well fitted by a convolution of a rectangular function with a biexponential clearance function. The parameters of the biexponential AIF model were found statistically different between MRI and PET. Pharmacokinetic MRI parameters such as the volume transfer constant (K(trans)), the extravascular-extracellular volume fraction (ν(e)), and the blood volume fraction (ν(p)) calculated with the Gd-DTPA AIF and the Gd-DTPA AIF converted from (18)F-FDG AIF normalized with or without blood sample were not statistically different. Similarly, the tumor metabolic rates of glucose (TMRGlc) calculated with (18) F-FDG AIF and with (18) F-FDG AIF obtained from Gd-DTPA AIF were also found not statistically different. In conclusion, only one accurate AIF would be needed for dual MRI-PET pharmacokinetic modeling in small animal models. PMID:22570280

  10. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

    Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet

    2016-01-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo. However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with 18F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer’s disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited 18F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was 18F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  11. 18F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis.

    Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose (18F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection

  12. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

    Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet; Hansson, Oskar

    2016-09-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  13. Design of an Automated System for Synthesis of [18 F] FDG for PET Investigation at IFIN-HH Bucharest

    Craciun, Liviu Stefan; Cimpeanu, Catalina; Constantinescu, Olimpiu; Dudu, Dorin; Ionescu, Cristina; Negoita, Nicolae; Racolta, Petru Mihai; Rusen, Ion

    2009-03-01

    A novel apparatus constructed at IFIN-HH is described for automated synthesis of radiopharmaceuticals labeled with 18F for use in positron emission tomography (PET) investigations. [18 F] fluoride was produced at the IFIN-HH cyclotron by irradiation of H2O enriched 97% in 18O with 13 MeV deuterons, or 8 MeV protons. The irradiated H2O was transferred (injected) into the radiochemical fully-automated processing systems which ensured the separation of 18F from H2O, the labeling with 18F, and finally purified by filtration with selective absorbants. The system is easy to operate and contains a programmable logical controller that manages the entire operation program stored in its internal memory. The computer is used to assist the operator during the different steps of synthesis and to allow visualization of the process and printing the report. The device was used for used for the production of 2-[18 F] FLUORO-2-DEOXY-D-GLUCOSE at the IFIN-HH cyclotron, one of the most used radiopharmaceutical in PET investigations. The synthesis module is configured so that is flexible enough to accomplish other nucleophile reactions of labeling with short lived radioisotopes.

  14. Secondary parkinsonism due to focal substantia nigra lesions. A PET study with [18F]FDG and [18F]fluorodopa

    We present a 71 year old woman with predominantly right sided parkinsonim of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [18F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [18F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions. (au) 39 refs

  15. Positron emission tomography with [18F]FDOPA and [18F]FDG in the imaging of small cell lung carcinoma: preliminary results

    Small cell lung carcinomas (SCLC) express neuroendocrine markers, and dihydroxyphenylalanine (DOPA) is known to accumulate in neuroendocrine tumours. This study was performed with the aim of evaluating the uptake of 3,4-dihydroxy-6-18F-fluoro-phenylalanine ([18F]FDOPA) by SCLC, based on comparison with the results of fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and standard imaging procedures. [18F]FDG PET and [18F]FDOPA PET were performed on four patients with newly diagnosed SCLC. There was agreement between the results of [18F]FDOPA PET and [18F]FDG PET in four tumoural sites out of 11, whereas [18F]FDG PET and standard imaging procedures were in full agreement. A semi-quantitative analysis based on standardised uptake values (SUVs) was performed in order to compare [18F]FDG and [18F]FDOPA tumour uptake. The median [18F]FDG SUVmax was 5.9 (with a 95% confidence interval from 4.4 to 9.2), while the median [18F]FDOPA SUVmax was 1.9 (with a 95% confidence interval from 1.6 to 3.8). The difference between [18F]FDG SUVmax and [18F]FDOPA SUVmax was significant (P18F]FDOPA PET appeared less sensitive than [18F]FDG PET and standard imaging procedures in the staging of SCLC. No clear relation between [18F]FDOPA uptake and positivity of neuroendocrine markers on immunohistochemistry emerged from these preliminary results; however, since [18F]FDOPA uptake may reflect better differentiation of the tumour, and possibly a better prognosis, this point warrants clarification in a larger study. (orig.)

  16. Synthesis and evaluation of 2-amino-5-(4-[18F]fluorophenyl)pent-4-ynoic acid ([18F]FPhPA): A novel 18F-labeled amino acid for oncologic PET imaging

    Introduction: 18 F-labeled amino acids are important PET radiotracers for molecular imaging of cancer. This study describes synthesis and radiopharmacological evaluation of 2-amino-5-(4-[18 F]fluorophenyl)pent-4-ynoic acid ([18 F]FPhPA) as a novel amino acid radiotracer for oncologic imaging. Methods: 18 F]FPhPA was prepared using Pd-mediated SONOGASHIRA cross-coupling reaction between 4-[18 F]fluoroiodobenzene ([18 F]FIB) and propargylglycine. The radiopharmacological profile of [18 F]FPhPA was evaluated in comparison with O-(2-[18 F]fluoroethyl)-L-tyrosine ([18 F]FET) using the murine breast cancer cell line EMT6 involving cellular uptake studies, radiotracer uptake competitive inhibition experiments and small animal PET imaging. Results: 18 F]FPhPA was prepared in 42 ± 10% decay-corrected radiochemical yield with high radiochemical purity >95% after semi-preparative HPLC purification. Cellular uptake of L-[18 F]FPhPA reached a maximum of 58 ± 14 % radioactivity/mg protein at 90 min. Lower uptake was observed for racemic and D-[18 F]FPhPA. Radiotracer uptake inhibition studies by synthetic and naturally occurring amino acids suggested that Na+-dependent system ASC, especially ASCT2, and Na+-independent system L are important amino acid transporters for [18 F]FPhPA uptake into EMT6 cells. Small animal PET studies demonstrated similar high tumor uptake of [18 F]FPhPA in EMT6 tumor-bearing mice compared to [18 F]FET reaching a maximum standardized uptake value (SUV) of 1.35 after 60 min p.i.. Muscle uptake of [18 F]FPhPA was higher (SUV30min = 0.65) compared to [18 F]FET (SUV30min = 0.40), whereas [18 F]FPhPA showed a more rapid uptake and clearance from the brain compared to [18 F]FET. Conclusion: L-[18 F]FPhPA is the first 18 F-labeled amino acid prepared through Pd-mediated cross-coupling reaction. Advances in Knowledge and Implications for patient Care: L-[18 F]FPhPA displayed promising properties as a novel amino acid radiotracer for molecular imaging of

  17. Comparative breast tumor imaging and comparative in vitro metabolism of 16α-[18F]Fluoroestradiol-17β and 16β-[18f]fluoromoxestrol in isolated hepatocytes

    16β-[18F]Fluoromoxestrol ([18F]βFMOX) is an analog of 16α-[18F]fluoroestradiol-17β ([18F]FES), a radiopharmaceutical known to be an effective positron emission tomography (PET) imaging agent for estrogen receptor-positive (ER+) human breast tumors. Based on comparisons of target tissue uptake efficiency and selectivity in a rat model, [18F]βFMOX was predicted to be as effective an imaging agent as [18F]FES. However, in a preliminary PET imaging study with [18F]βFMOX of 12 patients, 3 of whom had ER+ breast cancer, no tumor localization of [18F]βFMOX was observed. In search for an explanation for the unsuccessful [18F]βFMOX clinical trial, we have examined the rate of metabolism of [18F]βFMOX and [18F]FES in isolated rat, baboon, and human hepatocytes. We have also studied the effect of the serum protein sex hormone-binding globulin (SHBG), which binds [18F]FES better than [18F]βFMOX, on these rates of metabolism. Immature rat hepatocytes were found to metabolize [18F]FES 31 times faster than [18F]βFMOX, whereas mature rat cells metabolized [18F]FES only 3 times faster, and baboon and human hepatocytes only 2 times faster than [18F]βFMOX. In the presence of SHBG, the metabolic consumption rate for [18F]FES in mature rat hepatocytes decreased by 26%. Thus, the very favorable target tissue uptake characteristics of [18F]βFMOX determined in the rat probably result from its comparative resistance to metabolism (vis-a-vis [18F]FES) in this species, an advantage that is strongly reflected in comparative metabolism rates in rat hepatocytes. In the baboon and human, [18F]FES is extensively protein bound and protected from metabolism, an effect that may be reflected to a degree as a decrease in the rate of metabolism of this compound in baboon and human hepatocytes relative to [18F]βFMOX. Thus in primates, SHBG may potentiate the ER-mediated uptake of [18F]FES in ER+ tumors by selectively protecting this ligand from metabolism and ensuring its delivery to

  18. Microfluidic preparation of [18F]FE-SUPPY and [18F]FE-SUPPY:2 - comparison with conventional radiosyntheses

    Introduction: Recently, first applications of microfluidic principles for radiosyntheses of positron emission tomography compounds were presented, but direct comparisons with conventional methods were still missing. Therefore, our aims were (1) the set-up of a microfluidic procedure for the preparation of the recently developed adenosine A3-receptor tracers [18F]FE-SUPPY [5-(2-[18F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl) -6-phenylpyridine-5-carboxylate] and [18F]FE-SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[18F]fluoroethyl)sulfanylcarbonyl) -6-phenylpyridine-5-carboxylate] and (2) the direct comparison of reaction conditions and radiochemical yields of the no-carrier-added nucleophilic substitution with [18F]fluoride between microfluidic and conventional methods. Methods: For the determination of optimal reaction conditions within an Advion NanoTek synthesizer, 5-50 μl of precursor and dried [18F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (26oC-180oC) with defined reactant bolus flow rates (10-50 μl/min). Radiochemical incorporation yields (RCIYs) and overall radiochemical yields for large-scale preparations were compared with data from conventional batch-mode syntheses. Results: Optimal reaction parameters for the microfluidic set-up were determined as follows: 170oC, 30-μl/min pump rate per reactant (reaction overall flow rate of 60 μl/min) and 5-mg/ml precursor concentration in the reaction mixture. Applying these optimized conditions, we observed a significant increase in RCIY from 88.2% to 94.1% (P18F]FE-SUPPY and that from 42.5% to 95.5% (P18F]FE-SUPPY:2 using microfluidic instead of conventional heating. Precursor consumption was decreased from 7.5 and 10 mg to 1 mg per large-scale synthesis for both title compounds, respectively. Conclusion: The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic

  19. Parity Nonconservation in 18F, 19F, and 21Ne

    Haxton, W. C.; Gibson, B. F.; Henley, E. M.

    1980-11-01

    Parity nonconservation has been studied in 18F, 19F, and 21Ne for the Weinberg-Salam model. After careful treatment of nuclear structures aspects, values are predicted for the γ-ray asymmetry and circular polarizations in good agreement with experiment provided one employs meson-nucleon coupling constants somewhat weaker than the "best values" recently suggested by Desplanques, Donoghue, and Holstein.

  20. First results of the synthesis of [18F]FMHPU

    Substances labelled with positron emitters may become important for monitoring gene transfer of e.g. suicide genes. Our attempts to find new substances for monitoring gene expression led to a promising candidate, the pyrimidine derivative [18F]FMHPU. We investigated several reaction conditions in order to increase the radiochemical yield of the desired tracer. (orig.)

  1. 18F-fluorodeoxyglucose positron emission tomography in uterine carcinosarcoma

    Uterine carcinosarcomas clinically confined to the uterus usually harbor occult metastases. We conducted a pilot study to evaluate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in uterine carcinosarcoma. Patients with histologically confirmed uterine carcinosarcoma were enrolled. Abdominal and pelvic magnetic resonance imaging (MRI)/whole-body computed tomography (CT) scan, and whole-body 18F-FDG PET or PET/CT were undertaken for primary staging, evaluating response, and restaging/post-therapy surveillance. The clinical impact of 18F-FDG PET was determined on a scan basis. A total of 19 patients were recruited and 31 18F-FDG PET scans (including 8 scans performed on a PET/CT scanner) were performed. Positive impacts of scans were found in 36.8% (7/19) for primary staging, 66.7% (2/3) for monitoring response, and 11.1% (1/9) for restaging/post-therapy surveillance. PET excluded falsely inoperable disease defined by MRI in two patients. Aggressive treatment applying to three patients with PET-defined resectable stage IVB disease seemed futile. Two patients died of disease shortly after salvage therapy restaged by PET. With PET monitoring, one stage IVB patient treated by targeted therapy only was alive with good performance. Using PET did not lead to improvement of overall survival of this series compared with the historical control (n = 35) (P 0.779). The preliminary results suggest that 18F-FDG PET is beneficial in excluding falsely inoperable disease for curative therapy and in making a decision on palliation for better quality of life instead of aggressive treatment under the guidance of PET. PET seems to have limited value in post-therapy surveillance or restaging after failure. (orig.)

  2. 18F-Fluoride-PET in Skeletal Imaging

    Bone scintigraphy using 99mTc-labeled phosphate agents has long been the standard evaluation method for whole skeletal system. However, recent shortage of 99mTc supply and advanced positron emission tomography (PET) technology evoked the attention to surrogate radiopharmaceuticals and imaging modalities for bone. Actually, fluorine-18 (18F) was the first bone seeking radiotracer before the introduction of 99mTc-labeled agents even though its clinical application failed to become pervasive anymore after the rapid spread of Anger type gamma camera systems in early 1970s. However, rapidly developed PET technology made us refocus on the usefulness of 18F as a PET tracer. Early study comparing 18F-Na PET scan and planar bone scintigraphy reported that PET has higher sensitivity and specificity in the diagnosis of metastatic bone lesions than planar bone scan. Subsequent reports comparing between PET and both planar and SPECT bone image also revealed better results of PET scan in similar study groups. Rapid clinical application of PET/CT also accumulated considerable amount of experiences in skeletal evaluation and this modality is known to have better diagnostic power than stand alone PET system as well as bone scan. Furthermore 18F-Na PET/CT revealed better or at least equal results in detection of primary and metastatic bone lesions compared with CT and MRI. Therefore, it is obvious that 18F-Na PET/CT has potential to become new imaging modality for practical skeletal evaluation so continuous and careful evaluation of this modality and radiopharmaceutical must be required

  3. [18F] FDG PET in gastric non-Hodgkin's lymphoma

    The possibility of using [18F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [18F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [18F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [18F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [18F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy. (orig.)

  4. N-[{sup 18}f]fluoroethylpiperidinyl, n-[{sup 18}f]fluoroethylpiperidinemethyl and n-[{sup 18}f]fluoroethylpyrrolidinyl esters as radiotracers for acetylcholinesterase

    Shao Xia; Butch, Elizabeth R.; Kilbourn, Michael R.; Snyder, Scott E. E-mail: snyserse@umich.edu

    2003-05-01

    A series of N-fluoroethylpiperidinyl (1), N-fluoroethylpiperidinemethyl (2) and N-fluoroethylpyrrolidinyl (3) esters were synthesized and examined as new {sup 18}F-labeled radiotracers for measuring brain cholinesterase activity. The fluoroethyl group, instead of methyl group, results in slower in vitro enzymatic cleavage rates and higher selectivity for AChE. Based on metabolism in mouse blood and PET time-activity curves in rats, two radiotracers were identified as potential candidates for further in vivo evaluation in higher species.

  5. N-[18f]fluoroethylpiperidinyl, n-[18f]fluoroethylpiperidinemethyl and n-[18f]fluoroethylpyrrolidinyl esters as radiotracers for acetylcholinesterase

    A series of N-fluoroethylpiperidinyl (1), N-fluoroethylpiperidinemethyl (2) and N-fluoroethylpyrrolidinyl (3) esters were synthesized and examined as new 18F-labeled radiotracers for measuring brain cholinesterase activity. The fluoroethyl group, instead of methyl group, results in slower in vitro enzymatic cleavage rates and higher selectivity for AChE. Based on metabolism in mouse blood and PET time-activity curves in rats, two radiotracers were identified as potential candidates for further in vivo evaluation in higher species

  6. Functional evaluation of myocardial viability by 99mTc tetrofosmin gated SPECT. A quantitative comparison with 18F fluorodeoxyglucose positron emission CT (18F FDG PET)

    To validate functional analysis of gated SPECT in detecting myocardial viability, seventeen patients (male 15, female 2, mean age 58) with angiographically proven chronic ischemic heart disease (RCA 6, LAD 10, LCX 1) and eight normal volunteers (all male) were studied. All patients underwent 18F FDG PET and 99mTc tetrofosmin (TF) gated SPECT within a week. After being displayed in a polar map, myocardial perfusion was regionally determined by the mean count in 9 segments at end diastole (ED) and end systole (ES) in gated SPECT. Systolic function was determined by the count increase ratio from ED to ES (WTI: ES-ED/ED). Glucose metabolism was assessed by 18F FDG PET in the segments correspondent to those defined for SPECT. TF %uptake of <60% was defined as hypoperfusion, and FDG %uptake of <50% was defined as reduced glucose metabolism. The myocardial segments were classified into 3 categories: ''normal'' perfusion (n=85), ''mismatch'' (reduced perfusion with reserved FDG uptake, n=25) and ''matched'' reduced perfusion and metabolic reduction (n=26). Mean WTI in ''mismatch'' segment was 0.38±0.21, and was significantly greater than that in ''matched reduced'' segments, 0.15±0.20 (p<0.001). It was also greater than that in normal'' segments, 0.27±0.16. Regression analysis showed that association between WTI and FDG %uptake was significant (r=0.57, p<0.0005) for the ischemic segments (''mismatch''+''matched'', n=51), but the association was weak for the entire segments although it was statistically significant (r=0.26, p=0.02, n=136). For the segments determined as infarct by perfusion image, systolic functional analysis by gated SPECT is helpful in differentiation of a viable myocardial region or artifact from a scar. Nevertheless, further clinical and technical assessment is required for ECG gating to eliminate overestimation of viability and to warrant clinical use. (author)

  7. Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

    To retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. At least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p 18F-DOPA and 18F-FDG PET/CT (p 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p 18F-DOPA PET/CT and 18F-FDG PET/CT (p 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p 18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour. (orig.)

  8. (18)F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis.

    Keijsers, R.G.; Grutters, J.C.; Velzen-Blad, H. van; Bosch, J.M. van den; Oyen, W.J.G.; Verzijlbergen, F.J.

    2010-01-01

    PURPOSE: Bronchoalveolar lavage (BAL) and (18)F-fluorodeoxyglucose ((18)F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by (18)F-FDG PET represents signs of disease activity as reflected by BAL, (18)F-FDG PET patterns were compared with BAL cell profiles

  9. Simplified quantification and whole-body distribution of [18F]FE-PE2I in nonhuman primates: prediction for human studies

    Introduction: [18F]FE-PE2I is a promising dopamine transporter (DAT) radioligand. In nonhuman primates, we examined the accuracy of simplified quantification methods and the estimates of radiation dose of [18F]FE-PE2I. Methods: In the quantification study, binding potential (BPND) values previously reported in three rhesus monkeys using kinetic and graphical analyses of [18F]FE-PE2I were used for comparison. BPND using the cerebellum as reference region was obtained with four reference tissue methods applied to the [18F]FE-PE2I data that were compared with the kinetic and graphical analyses. In the whole-body study, estimates of adsorbed radiation were obtained in two cynomolgus monkeys. Results: All reference tissue methods provided BPND values within 5% of the values obtained with the kinetic and graphical analyses. The shortest imaging time for stable BPND estimation was 54 min. The average effective dose of [18F]FE-PE2I was 0.021 mSv/MBq, similar to 2-deoxy-2-[18F]fluoro-D-glucose. Conclusions: The results in nonhuman primates suggest that [18F]FE-PE2I is suitable for accurate and stable DAT quantification, and its radiation dose estimates would allow for a maximal administered radioactivity of 476 MBq in human subjects.

  10. Stereotactic Comparison Study of 18F-Alfatide and 18F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model

    Wei, Yu-Chun; Gao, Yongsheng; Zhang, Jianbo; Fu, Zheng; Zheng, Jinsong; Liu, Ning; Hu, Xudong; Hou, Wenhong; Yu, Jinming; Yuan, Shuanghu

    2016-01-01

    This study aimed to stereotactically compare the PET imaging performance of 18F-Alfatide (18F-ALF-NOTA-PRGD2, denoted as 18F-Alfatide) and 18F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. 18F-FDG standard uptake values (SUVs) were higher than 18F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of 18F-Alfatide PET were significantly higher than those of 18F-FDG PET (P SUV and GLUT-1 (R = 0.895, P SUV and αvβ3 (R = 0.595, P = 0.019), 18F-FDG SUV and 18F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvβ3 (R = 0.637, P = 0.011). Therefore, 18F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to 18F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study. PMID:27350554

  11. Stereotactic Comparison Study of (18)F-Alfatide and (18)F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model.

    Wei, Yu-Chun; Gao, Yongsheng; Zhang, Jianbo; Fu, Zheng; Zheng, Jinsong; Liu, Ning; Hu, Xudong; Hou, Wenhong; Yu, Jinming; Yuan, Shuanghu

    2016-01-01

    This study aimed to stereotactically compare the PET imaging performance of (18)F-Alfatide ((18)F-ALF-NOTA-PRGD2, denoted as (18)F-Alfatide) and (18)F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. (18)F-FDG standard uptake values (SUVs) were higher than (18)F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of (18)F-Alfatide PET were significantly higher than those of (18)F-FDG PET (P SUV and GLUT-1 (R = 0.895, P SUV and αvβ3 (R = 0.595, P = 0.019), (18)F-FDG SUV and (18)F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvβ3 (R = 0.637, P = 0.011). Therefore, (18)F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to (18)F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study. PMID:27350554

  12. Role of 18F-FDG PET Scan in Rheumatoid Lung Nodule: Case Report and Review of the Literature

    Lohr, Kristine M.; Chhakchhuak, Christine L.; Mehdi Khosravi

    2013-01-01

    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 ei...

  13. Intense uptake evidenced by 18F-FDG PET/CT without a corresponding CT finding--dream or reality?

    Caobelli, Federico; Pizzocaro, Claudio; Guerra, Ugo Paolo

    2014-01-01

    Although 18F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) has been widely validated and extensively used in the latest years in clinical practice, interpretation of PET/CT images can be affected by several pitfalls. We here present a case of intense lung uptake in a patient without a corresponding finding on CT images, probably due to a microembolism produced during the injection process and located in small vascular structures of the lung parenchyma. PMID:24610649

  14. Standardization of 18F by digital coincidence counting

    The radioactivity of 18F has been measured by a digital coincidence counting (DCC) system. The main advantages of the digital coincidence counting technique are a shortening of the measurement time as compared with conventional coincidence counting and an ability to obtain activities with various experimental parameters through off-line analysis. The measurement results of radioactivity for 18F solution were compared with those of a conventional coincidence counting technique and a reference ion chamber method. - Highlights: ► Radioactivity of F-18 is measured by a DCC technique. ► DCC technique has an advantage for the radionuclide with short half-life. ► Activity results show a good agreement with those of other methods.

  15. Does diabetes affect [{sup 18}F]FDG standardised uptake values in lung cancer?

    Gorenberg, Miguel [Department of Nuclear Medicine, Rebecca Sieff Government Hospital, Safed (Israel); Hallett, William A.; O' Doherty, Michael J. [Clinical PET Centre, Guy' s, King' s and St Thomas' School of Medicine, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH (United Kingdom)

    2002-10-01

    The correlation of hyperglycaemia with decreased 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumours in positron emission tomography (PET) imaging has been clearly established. The available data are mainly based on non-diabetic (non-DM) patients exposed to acute hyperglycaemia after glucose infusion, and little is known about the effect of diabetes mellitus (DM) on FDG uptake by tumours. In this retrospective study we performed a comparison of the tumour uptake in 40 DM patients with the tumour uptake in 145 non-DM patients, all with primary lung malignancies. Peak standardised uptake values (SUVs) without glucose correction were calculated for the lung lesions. Mean ({+-}standard deviation) blood glucose concentrations were 6.58{+-}2.46 mmol/l in the DM patients and 4.39{+-}0.89 mmol/l in the non-DM patients. There was no significant difference between tumour SUVs in DM patients (79 lesions), 5.86{+-}3.97, and those in non-DM patients (234 lesions), 6.47{+-}4.61. There was no significant difference between tumour SUVs in DM patients with blood glucose <7 mmol/l (n=28, 64 lesions), 5.91{+-}3.98, and those in DM patients with blood glucose >7 mmol/l (n=12, 15 lesions), 5.68{+-}4.09. There was also no significant difference between myocardial SUVs in the DM patients (n=40), 3.28{+-}2.75, and in a similar group of non-DM patients (n=42), 3.30{+-}2.24. We conclude that FDG uptake in lung tumours is not significantly influenced by blood glucose levels in diabetic patients whose blood glucose levels are reasonably well controlled. (orig.)

  16. [18F]FDG-PET in lung cancer: current status

    Jane Dobbs, H; Quint, Leslie Eisenbud; Miles, K A

    2005-01-01

    Increasingly, evidence of safety, effectiveness and cost-effectiveness is required to support funding of new diagnostic technologies. However, diagnostic imaging is a rapidly changing speciality with new data constantly being added to the evidence base. This article aims to review the evidence base for the application of fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in lung cancer and to identify areas in which the evidence base is evolving. Currently, there is strong evidenc...

  17. Synthesis and evaluation of 18F-labeled PPARγ antagonists

    Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) transcriptionally modulates fat metabolism and also plays a role in pathological conditions such as cancer, neurodegenerative disease and inflammation. PPARγ imaging agents are potential tools for investigating these diseases. Methods: Four analogs of GW9662, a PPARγ antagonist, with different fluorine-containing substituents at the para-position of the aniline ring were synthesized and evaluated using two different receptor binding assays for measuring PPARγ affinity. Micro-positron emission tomography (PET) imaging studies were performed in a transgenic mouse model having a heart-specific overexpression of PPARγ. Results: All four analogs were found to have binding affinities that were comparable to or better than the reference antagonist, GW9662, using a scintillation proximity assay (SPA). However, only the chloro-based analogs (compounds 3 and 4) had activity in a whole-cell assay measuring activation of the PPARγ/retinoid X receptor complex. The microPET imaging studies in an MHC-PPARγ transgenic mouse model showed high uptake and PPARγ-specific binding for the irreversible antagonist [18F]3, whereas the corresponding reversible methoxy analog ([18F]5) displayed only nonspecific uptake in heart. Conclusions: The results of this preliminary study show that the irreversible antagonist [18F]3 may represent a novel strategy for imaging PPARγ in vivo with PET.

  18. CHARACTERIZATION OF TANK 18F WALL AND SCALE SAMPLES

    Hay, Michael; Click, Damon; Diprete, c.; Diprete, David

    2010-03-01

    Samples from the wall of Tank 18F were obtained to determine the associated source term using a special wall sampling device. Two wall samples and a scale sample were obtained and characterized at the Savannah River National Laboratory (SRNL). All the analyses of the Tank 18F wall and scale samples met the targeted detection limits. The upper wall samples show {approx}2X to 6X higher concentrations for U, Pu, and Np on an activity per surface area basis than the lower wall samples. On an activity per mass basis, the upper and lower wall samples show similar compositions for U and Pu. The Np activity is still {approx}2.5X higher in the upper wall sample on a per mass basis. The scale sample contains 2-3X higher concentrations of U, Pu, and Sr-90 than the wall samples on an activity per mass basis. The plutonium isotopics differ for all three wall samples (upper, lower, and scale samples). The Pu-238 appears to increase as a proportion of total plutonium as you move up the tank wall from the lowest sample (scale sample) to the upper wall sample. The elemental composition of the scale sample appears similar to other F-Area PUREX sludge compositions. The composition of the scale sample is markedly different than the material on the floor of Tank 18F. However, the scale sample shows elevated Mg and Ca concentrations relative to typical PUREX sludge as do the floor samples.

  19. 18F in hot atom chemistry and equilibrium chemical kinetics

    Superexcited molecules are unusual species that at present can only be investigated using nuclear recoil methods. The thermochemical technique for measuring the excitation energy distributions of superexcited molecules is reviewed and applied to recent studies of CF318F and C2F518F formed from high energy atomic exchange reactions in CF4 and C2F6. The nascent CF318F and C2F518F range in energy from 1.7 to about 45 eV. The average energies of these products range from 15 to 20 eV. The internal excitation that accompanies these reactions is initially localized near the 18F bonding site, and the C2F518F decomposition mechanism is non-statistical. Moderated nuclear recoil experiments yield mechanisms and rates for the reactions of thermal 18F atoms. Under our standard experimental conditions from 3.4 x 104 to 3.4 x 108 labeled product molecules are available for radioassay. This procedure is free from systematic error and the measurements yield exceptional precision and sensitivity because (1) high energy reactions with the thermally active reagents are suppressed. (2) the host environment is rigorously controlled, and (3) the molecular products from many single atom reactions are directly counted. The limitations of this technique are described and results are presented for the reactions of thermal 18F atoms with CH4 and C2H4. (J.P.N.)

  20. [18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

    Introduction: Transport of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood–brain barrier (BBB) may confound the interpretation of [18F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [18F]FDG in vivo by performing [18F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [18F]FDG brain distribution after transporter inhibition. Methods: Dynamic small-animal PET experiments (60 min) were performed with [18F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b(−/−), Abcg2(−/−) and Abcb1a/b(−/−)Abcg2(−/−)) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15 mg/kg, given at 2 h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [18F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (Kb,brain). Results: Kb,brain values of [18F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [18F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but Kb,brain values were not significantly different between both rat groups. Conclusion: Our results show that [18F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [18F]FDG at the mouse BBB. Advances in knowledge and implications for patient care: Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when interpreting brain [18F]FDG PET data

  1. A Comparative Study of Noninvasive Hypoxia Imaging with 18F-Fluoroerythronitroimidazole and 18F-Fluoromisonidazole PET/CT in Patients with Lung Cancer.

    Yuchun Wei

    Full Text Available This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM and 18F-fluoromisonidazole (18F-FMISO positron emission tomography/computed tomography (PET/CT in patients with inoperable stages III-IV lung cancer.A total of forty-two patients with inoperable stages III-IV lung cancer underwent 18F-FETNIM PET/CT (n = 18 and 18F-FMISO PET/CT (n = 24 before chemo/radiation therapy. The standard uptake values (SUVs of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B were used to quantify hypoxia.All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54, as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33 were seen in tumor, P = 0.022, 5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029, whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707. Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02.18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer.

  2. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial 18F-FDG Uptake in Normal Humans

    In a whole-body 18F-FDG PET/CT, non-specific 18F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial 18F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before 18F-FDG injection from all subjects. Myocardial 18F-FDG uptake was measured as the mean (SUVmean) and maximal (SUVmax) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUVmax was 4.57, respectively and there was a strong linear correlation between SUVmean and SUVmax (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial 18F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial 18F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve 18F-FDG PET/CT imaging for specific oncologic and cardiovascular indications

  3. (18)F-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease.

    Rokka, Johanna; Snellman, Anniina; Kaasalainen, Martti; Salonen, Jarno; Zona, Cristiano; La Ferla, Barbara; Nicotra, Francesco; Re, Francesca; Masserini, Massimo; Forsback, Sarita; Lopez-Picon, Francisco; Rinne, Juha O; Haaparanta-Solin, Merja; Solin, Olof

    2016-06-10

    The aim of the present study was to synthesize functionalized (18)F-labeled NLs ((18)F-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. (18)F-fluorine was introduced to (18)F-NLs either by using a core forming (18)F-lipid or by encapsulating a (18)F-tracer, (18)F-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized (18)F-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and β-amyloid plaque-binding ability of (18)F-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60min after (18)F-NL injection. Functionalized (18)F-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of (18)F-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of (18)F-NLs but the overall brain uptake remained low with all functionalized (18)F-NLs. The liposomal encapsulation of (18)F-treg-curcumin was not successful and preclinical results of encapsulated (18)F-treg-curcumin and plain (18)F-treg-curcumin were identical. Although the studied functionalized (18)F-NLs were not suitable for PET imaging as such, the synthesis techniques introduced in this study can be utilized to modify the biological behavior of (18)F-labeled NLs. PMID:26993963

  4. {sup 18}F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

    Koo, Hye Ryoung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Hanyang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, Jeong Seon [Hanyang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kang, Keon Wook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Cho, Nariya; Chang, Jung Min; Bae, Min Sun; Kim, Won Hwa; Lee, Su Hyun; Seo, Mirinae; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Mi Young [Konkuk University Medical Center, Department of Radiology, Seoul (Korea, Republic of); Kim, Jin You [Pusan National University Hospital, Department of Radiology, Pusan (Korea, Republic of)

    2014-03-15

    To determine whether a correlation exists between maximum standardized uptake value (SUV{sub max}) on {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer. This retrospective study involved 548 patients (mean age 51.6 years, range 21-81 years) with 552 index breast cancers (mean size 2.57 cm, range 1.0-14.5 cm). The correlation between {sup 18}F-FDG uptake in PET/CT, expressed as SUV{sub max}, and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed. The mean SUV{sub max} value of the 552 tumours was 6.07 ± 4.63 (range 0.9-32.8). The subtypes of the 552 tumours were 334 (60 %) luminal A, 66 (12 %) luminal B, 60 (11 %) HER2 positive and 92 (17 %) triple negative, for which the mean SUV{sub max} values were 4.69 ± 3.45, 6.51 ± 4.18, 7.44 ± 4.73 and 9.83 ± 6.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (P < 0.001) and 1.27-fold (P = 0.009) higher SUV{sub max} values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade. FDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUV{sub max} values than luminal A tumours. circle {sup 18} F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers. (orig.)

  5. Does diabetes affect [18F]FDG standardised uptake values in lung cancer?

    The correlation of hyperglycaemia with decreased 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumours in positron emission tomography (PET) imaging has been clearly established. The available data are mainly based on non-diabetic (non-DM) patients exposed to acute hyperglycaemia after glucose infusion, and little is known about the effect of diabetes mellitus (DM) on FDG uptake by tumours. In this retrospective study we performed a comparison of the tumour uptake in 40 DM patients with the tumour uptake in 145 non-DM patients, all with primary lung malignancies. Peak standardised uptake values (SUVs) without glucose correction were calculated for the lung lesions. Mean (±standard deviation) blood glucose concentrations were 6.58±2.46 mmol/l in the DM patients and 4.39±0.89 mmol/l in the non-DM patients. There was no significant difference between tumour SUVs in DM patients (79 lesions), 5.86±3.97, and those in non-DM patients (234 lesions), 6.47±4.61. There was no significant difference between tumour SUVs in DM patients with blood glucose 7 mmol/l (n=12, 15 lesions), 5.68±4.09. There was also no significant difference between myocardial SUVs in the DM patients (n=40), 3.28±2.75, and in a similar group of non-DM patients (n=42), 3.30±2.24. We conclude that FDG uptake in lung tumours is not significantly influenced by blood glucose levels in diabetic patients whose blood glucose levels are reasonably well controlled. (orig.)

  6. 18F-FDG PET/CT is a valuable tool for relapsing polychondritis diagnose and therapeutic response monitoring

    To retrospectively investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis and therapeutic response in relapsing polychondritis (RP) patients. 18F-FDG PET/CT findings were reviewed in six RP patients. The initial scans were performed for all patients, follow-up scans were performed during steroid therapy for five patients. Changes in the abnormal lesions and the maximal standard uptake value (SUVmax) were analyzed. The initial PET/CT scans revealed intense FDG uptake in the cartilages for all six patients. The lesions of abnormal FDG uptake were tracheal/bronchial cartilage (n=4), costicartilage (n=4), nasal cartilage (n=3), cricoid cartilage (n=3), auricular cartilage (n=3), arytenoid cartilage (n=3), thyroid cartilage (n=2), hyoid cartilage (n=1) and mediastinum lymph node (n=1). The mean visual score and the mean SUVmax were 2.96 ± 0.20 and 4.10 ± 0.6. The intense uptake reduced or disappeared during steroid therapy for five patients, the mean visual score and the mean SUVmax were 1.58 ± 1.4 and 1.51 ± 1.4. 18F-FDG PET/CT enables the acquisition of both morphologic and glucose metabolic of the related cartilage structures. It plays a valuable role in assessing almost all cartilage and detecting RP, which is a better selection of a biopsy site as well as therapeutic response monitoring. (author)

  7. Evolving role of 18F-FDG-PET/CT for the body tumor and metastases in pediatrics

    18F-FDG-positron emission tomography-computerized tomography (18F-FDG-PET/CT) scan is an important imaging tool which may provide both functional and anatomical information in a single diagnostic test. It has the potential to be a valuable tool in the noninvasive evaluation and monitoring of pediatric tumors including the metastases because 18fluorodeoxyglucose (18F-FDG) is a glucose analogue that concentrates in areas of active metabolic activity. This review provides an update on functional and metabolic imaging approaches for assessment and management of the body tumor and metastases in pediatrics using a combined whole body 18F-FDG-PET/CT scanners. We discuss the benefits include improved pediatric patients' outcome facilitated by staging and monitoring of disease and better treatment planning. It is worth to concern the preparation of children undergoing PET studies and radiation dosimetry and its implications for family and caregivers. It is important to consider the normal distribution of 18FDG in children, common variations of the normal distribution. We show some of our cases that most tumors in children accumulate and retain FDG, allowing high-quality images of their distribution and pathophysiology either at the primary site as well as in the areas of metastatic disease.

  8. Evolving role of {sup 18}F-FDG-PET/CT for the body tumor and metastases in pediatrics

    Chen Zhengguang, E-mail: guangchen1@gmail.co [Department of Radiology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, No. 5 Hai Yun Cang Beijing 100700 (China); Li Xiaozhen, E-mail: lixiaozhen79@gmail.co [Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shui Fu Yuan, Wang Fu Jing Da Jie, Beijing 100730 (China); Li Fang, E-mail: lifang@gmail.co [Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shui Fu Yuan, Wang Fu Jing Da Jie, Beijing 100730 (China); Ouyang Qiaohong [Department of Nuclear Medicine, First Affiliated Hospital, PLA General Hospital, Beijing 100853 (China); Yu Tong [Imaging Center, Beijing Children' s Hospital Affiliated to Capital Medical University. 56, Nanlishi Road, Xicheng District, Beijing 100045 (China)

    2010-09-15

    {sup 18}F-FDG-positron emission tomography-computerized tomography ({sup 18}F-FDG-PET/CT) scan is an important imaging tool which may provide both functional and anatomical information in a single diagnostic test. It has the potential to be a valuable tool in the noninvasive evaluation and monitoring of pediatric tumors including the metastases because {sup 18}fluorodeoxyglucose ({sup 18}F-FDG) is a glucose analogue that concentrates in areas of active metabolic activity. This review provides an update on functional and metabolic imaging approaches for assessment and management of the body tumor and metastases in pediatrics using a combined whole body {sup 18}F-FDG-PET/CT scanners. We discuss the benefits include improved pediatric patients' outcome facilitated by staging and monitoring of disease and better treatment planning. It is worth to concern the preparation of children undergoing PET studies and radiation dosimetry and its implications for family and caregivers. It is important to consider the normal distribution of {sup 18}FDG in children, common variations of the normal distribution. We show some of our cases that most tumors in children accumulate and retain FDG, allowing high-quality images of their distribution and pathophysiology either at the primary site as well as in the areas of metastatic disease.

  9. [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study

    Asadpour Branka

    2006-03-01

    Full Text Available Abstract Background Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([18F] Fluoromisonidazole (FMISO and [18F]-2-fluoro-2'-deoxyglucose (FDG PET. Methods Eight patients with non-small-cell lung cancer underwent PET scans. Tumour tissue oxygenation was measured with FMISO PET, whereas tumour glucose metabolism was measured with FDG PET. All PET studies were carried out with an ECAT EXACT 922/47® scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 180 min after intravenous administration of the tracer. The acquisition and reconstruction parameters were as follows: 30 min emission scanning and 4 min transmission scanning with 68-Ge/68-Ga rod sources. The patients were treated with chemotherapy, consisting of 2 cycles of gemcitabine (1200 mg/m2 and vinorelbine (30 mg/m2 followed by concurrent radio- (2.0 Gy/d; total dose 66.0 Gy and chemotherapy with gemcitabine (300–500 mg/m2 every two weeks. FMISO PET and FDG PET were performed in all patients 3 days before and 14 days after finishing chemotherapy. Results FMISO PET allowed for the qualitative and quantitative definition of hypoxic sub-areas which may correspond to a localization of local recurrences. In addition, changes in FMISO and FDG PET measure the early response to therapy, and in this way, may predict freedom from disease, as well as overall survival. Conclusion These preliminary results warrant validation in larger trials. If confirmed, several novel treatment strategies may be considered, including the early use of PET to evaluate the effectiveness of the selected therapy.

  10. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

    The nucleoside analogue 3'-deoxy-3'-18F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-18F-fluoro-D-glucose (FDG). A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake. (orig.)

  11. A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma.

    Costantini, Danny L; Vali, Reza; McQuattie, Susan; Chan, Jeffrey; Punnett, Angela; Weitzman, Shiela; Shammas, Amer; Charron, Martin

    2016-01-01

    We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6 ± 0.6 and 5.0 ± 0.3, versus 18F-FDG SUV 1.9 ± 0.1 and 3.4 ± 0.7, resp., p SUVs of 2.6 ± 0.1 and 2.0 ± 0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned. PMID:27313888

  12. Usefulness of dynamic 18F-FDG PET scan in lung cancer and inflammation disease

    The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (18F-FDG PET) for the non-invasive differentiation of focal lung lesions originated from cancer or inflammation disease by combined visual image interpretation and semi-quantitative uptake value analysis has been documented. In general, Standardized Uptake Value (SUV) is used to diagnose lung disease. But SUV dose not contain dynamic information of lung tissue for the glucose. Therefore, this study was undertaken to hypothesis that analysis of dynamic kinetics of focal lung lesions base on 18F-FDG PET may more accurately determine the lung disease. So we compared Time Activity Curve (TAC), Standardized Uptake Value-Dynamic Curve (SUV-DC) graph pattern with Glucose Metabolic Rate (MRGlu) from Patlak analysis. With lung disease, 17 patients were examined. They were injected with 18F-FDG over 30-s into peripheral vein while acquisition of the serial transaxial tomographic images were started. For acquisition protocol, we used twelve 10-s, four 30-s, sixteen 60-s, five 300-s and one 900-s frame for 60 mins. Its images were analyzed by visual interpretation TAC, SUV-DC and a kinetic analysis (Patlak analysis). The latter was based on region of interest (ROIs) which were drawn with the lung disease shape. Each optimized patterns were compared with itself. In TAC patterns, it hard to observe cancer type with inflammation disease in early pool blood area but over the time cancer type slope more remarkably increased than inflammation disease. SUV-DC was similar to TAC pattern. In the result of Patlak analysis, In time activity curve of aorta, even though inflammation disease showed higher blood activity than cancer, at first as time went by, blood activity of inflammation disease became the lowest. However, in time activity curve of tissue, cancer had the highest uptake and inflammation disease was in the middle. Through the examination, TAC and SUV-DC could approached the results that lung

  13. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a {sup 18}F-FDG PET/CT study

    Chiaravalloti, Agostino; Di Pietro, Barbara [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Department of Nuclear Medicine Karolinska Hospital Stockholm, Stockholm (Sweden); Micarelli, Alessandro; Alessandrini, Marco [University Tor Vergata, Department of Medical Science and Translational Medicine, Rome (Italy); Genovesi, Giuseppe [University La Sapienza, Department of Experimental Medicine, Rome (Italy); University La Sapienza, Regional Center for Diagnosis, Treatment and Prevention of MCS, Rome (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); IRCCS Neuromed, Pozzilli (Italy)

    2015-04-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two {sup 18}F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in {sup 18}F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation. (orig.)

  14. PET/CT studies of multiple myeloma using 18F-FDG and 18F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

    The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose (18F-FDG) and fluorine-18 sodium fluoride (18F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions. The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased 18F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the 18F-NaF PET/CT scans were then correlated with those detected on 18F-FDG PET/CT, which served as a reference. Moreover, the 18F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach. Whole body 18F-FDG PET/CT revealed approximately 343 focal lesions while 18F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in 18F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with 18F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal 18F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with 18F-NaF PET/CT. In three patients with multiple focal 18F-FDG-uptake, 18F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with 18F-FDG and 18F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of 18F-FDG revealed the following mean values: SUVaver = 5.1, k1 = 0.37 (1/min), k3 = 0.10 (1/min), VB = 0.06, influx = 0.04 (1/min

  15. Comparison of 18F-AIF-NOTA-PRGD2 and 18F-FDG uptake in lymph node metastasis of differentiated thyroid cancer.

    Weiwei Cheng

    Full Text Available A widespread application of integrin αvβ3 imaging has been emerging in both pre-clinical and clinical studies. But few studies reported its value as compared with 18F-FDG PET, especially for differentiated thyroid cancer (DTC. In this study, we compared the tracer uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG in lymph node metastasis of DTC to evaluate 18F-AIF-NOTA-PRGD2 as compared with 18F-FDG.20 DTC patients with presumptive lymph node metastasis were examined with 18F-AIF-NOTA-PRGD2 and 18F-FDG PET/CT. 16 patients undergoing fine needle aspiration biopsy (FNAB were evaluated by cytology results. For lesions without FNAB, the findings of clinical staging procedures served as the standard of reference (including neck ultrasound and serum thyroglobulin.A total of 39 presumptive lymph node metastases were visualized on PET/CT images. 35 lesions were confirmed as malignant by FNAB and other clinical findings. The mean 18F-AIF-NOTA-PRGD2 in radioactive iodine-refractory (RAIR lesions and benign lesions were 2.5±0.9 and 2.8±0.9 respectively. The mean SUV for 18F-FDG in all malignant lesions was 4.5±1.6 while in benign lesions it was 3.3±1.2. For all malignant lesions, the mean SUV for 18F-FDG was significantly higher than that for 18F-AIF-NOTA-PRGD2 (P<0.05. No significant correlation was found between the SUVs of 18F-AIF-NOTA-PRGD2 and 18F-FDG for 35 lesions (r = 0.114, P = 0.515. Moreover, 15 lesions of which the diameter larger than 1.5 cm had higher 18F-AIF-NOTA-PRGD2 uptake as compared with the lesions smaller than 1.5 cm.Although most lymph node metastases of DTC showed abnormal uptake of 18F-AIF-NOTA-PRGD2, its diagnostic value was inferior to 18F-FDG. No correlation was found between the uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG, which may suggest the two tracers provide complementary information in DTC lesions.

  16. Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples

    Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [18F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [18F]fluoride in biological samples. Methods: Low levels of [18F]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [18F]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [18F]Fluoride was also determined in plasma and urine from mice injected with [18F]-labeled thymidine analogues using Method A. Results: The detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075±0.004 vs. 0.71±0.02 nCi). With Method A, [18F]fluoride was determined in plasma for [18F]FLT, [18F]FMAU, [18F]FEAU and N3-[18F]FPrT as 1.4±0.31% (n=4), 0.17±0.49% (n=3), 4.88±1.62% (n=3) and 12.94±0.48% (n=4), respectively. The amount of [18F]fluoride determined in the urine was 11.49±1.60% (n=4) from [18F]FLT, 5.36±2.34% (n=3) from [18F]FMAU, 13.57±1.96% (n=3) from [18F]FEAU and 11.19±1.98% (n=4) from N3-[18F]FPrT. Conclusion: Low levels of [18F]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C18 column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [18F]-labeled radiotracer and PET.

  17. 18F-FDG PET in children with lymphomas

    The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in children with lymphomas, at various stages of their disease. Twenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin's disease (HD, n=17) or non-Hodgkin's lymphoma (NHL, n=11) were evaluated. Patients were investigated at initial staging (n=19), early in the course of treatment (n=19), at the end of treatment (n=16) and during long-term follow-up (n=19). A total of 113 whole-body PET studies were performed on dedicated scanners. PET results were compared with the results of conventional methods (CMs) such as physical examination, laboratory studies, chest X-rays, computed tomography, magnetic resonance imaging, ultrasonography and bone scan when available. At initial evaluation (group 1), PET changed the disease stage and treatment in 10.5% of the cases. In early evaluation of the response to treatment (group 2), PET failed to predict two relapses and one incomplete response to treatment. In this group, however, PET did not show any false positive results. There were only 4/75 false positive results for PET among patients studied at the end of treatment (group 3, specificity 94%) or during the systematic follow-up (group 4, specificity 95%), as compared with 27/75 for CMs (specificity 54% and 66%, respectively). 18F-FDG-PET is a useful tool for evaluating children with lymphomas. Large prospective studies are needed to appreciate its real impact on patient management. (orig.)

  18. Radiolabeling of [18F]altanserin — a microfluidic approach

    Introduction: Our aim was the optimization of radiochemical parameters for the microfluidic preparation of [18F]altanserin. The four main parameters evaluated were (1) precursor concentration, (2) reaction temperature, (3) bolus flow rate through the microreactor and (4) bolus volume. Methods: For the determination of optimal reaction conditions within a flow-through microreactor synthesizer, 5–400 μL of precursor and dried [18F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (180–220 °C) with defined bolus flow rates of 10–60 μL/min. Radiochemical incorporation yields (RCIYs) were examined using a thin layer chromatography (TLC) set-up and radio- high-performance liquid chromatography (HPLC). Results: Optimum reaction parameters for the microfluidic set-up were determined as following: 220 °C, 5–10 μL/min pump rate per reactant (10–20 μL/min reaction overall flow rate) and 2 mg/mL precursor concentration in the reaction mixture. Applying these optimized conditions, RCIYs of 53.7 ± 7.9 were observed for scaled-up preparations. A positive “bolus effect” was observed: applying higher reaction volume resulted in increased RCIYs. Conclusion: This study proved that the reaction bolus volume is an essential parameter influencing the RCIY of [18F]altanserin. A possible explanation is the inhomogeneous distribution within the reaction volume probably caused by diffusion at the bolus interface. This important finding should be considered an important variable for the evaluation of all novel radiotracers labeled using a flow-through reactor device.

  19. Acute and subacute toxicity of 18F-FDG

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  20. {sup 18}F-FDG PET in children with lymphomas

    Depas, Gisele; Barsy, Caroline De; Foidart, Jacqueline; Rigo, Pierre; Hustinx, Roland [University Hospital, Division of Nuclear Medicine, Liege (Belgium); Jerusalem, Guy [University Hospital, Division of Medical Oncology, Liege (Belgium); Hoyoux, Claire; Dresse, Marie-Francoise [CHR Citadelle, Division of Pediatric Hematology and Oncology, Liege (Belgium); Fassotte, Marie-France [University Hospital, Division of Hematology, Liege (Belgium); Paquet, Nancy [Hotel de Dieu, Levis, Division of Nuclear Medicine, Quebec (Canada)

    2005-01-01

    The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) in children with lymphomas, at various stages of their disease. Twenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin's disease (HD, n=17) or non-Hodgkin's lymphoma (NHL, n=11) were evaluated. Patients were investigated at initial staging (n=19), early in the course of treatment (n=19), at the end of treatment (n=16) and during long-term follow-up (n=19). A total of 113 whole-body PET studies were performed on dedicated scanners. PET results were compared with the results of conventional methods (CMs) such as physical examination, laboratory studies, chest X-rays, computed tomography, magnetic resonance imaging, ultrasonography and bone scan when available. At initial evaluation (group 1), PET changed the disease stage and treatment in 10.5% of the cases. In early evaluation of the response to treatment (group 2), PET failed to predict two relapses and one incomplete response to treatment. In this group, however, PET did not show any false positive results. There were only 4/75 false positive results for PET among patients studied at the end of treatment (group 3, specificity 94%) or during the systematic follow-up (group 4, specificity 95%), as compared with 27/75 for CMs (specificity 54% and 66%, respectively). {sup 18}F-FDG-PET is a useful tool for evaluating children with lymphomas. Large prospective studies are needed to appreciate its real impact on patient management. (orig.)

  1. Critical considerations on the combined use of {sup 18}F-FDG and {sup 18}F-fluoride for PET assessment of metastatic bone disease

    Cheng, Gang [Philadelphia VA Medical Center, Department of Radiology, Philadelphia, PA (United States); Hospital of the University of Pennsylvania, Division of Nuclear Medicine, Department of Radiology, Philadelphia, PA (United States); Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Basu, Sandip [Tata Memorial Hospital Annexe, Radiation Medicine Centre (Bhabha Atomic Research Centre), Parel, Bombay (India); Alavi, Abass [Hospital of the University of Pennsylvania, Division of Nuclear Medicine, Department of Radiology, Philadelphia, PA (United States)

    2013-08-15

    {sup 18}F-FDG PET/CT is a reliable imaging tool in the detection of osseous metastasis in most cases. Adedicated bone scan (including {sup 18}F-fluoride PET/CT) may not be indicated in many cancers for the evaluation of osseous metastasis, especially at early stages. Combined use of dual tracers may compromise the imaging quality of both studies, especially for 1sF-FDG PET with respect to its ability to detect lesions in the bone marrow. The authors have no doubt that {sup 18}F-fluoride PET may be valuable and provide some additional value in some selected cases and selected cancers, where {sup 18}F-FDG is of limited value. However, the value of using the combined approach is limited in most situations. The logical notion, is that for {sup 18}F-FDG-avid tumors, there is no evidence in the literature that {sup 18}F-fluoride PET/CT detects more osseous lesions than {sup 18}F-FDG PET/CT, while for non-t8F-FDc-avid tumors, {sup 18}F-FDG PET/CT is not indicated. Both the rare occasions (when both {sup 18}F-FDG PET and {sup 18}F-fluoride PET are indicated) and the advantages of performing a dual tracer PET remain to be defined.

  2. Synthesis of n.c.a. 18F-fluorinated NMDA- and D4-receptor ligands via [18F]fluorobenzenes

    In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) 18F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. (±)-3-(4-hydroxy-4-(4-[18F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[18F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([18F]FPTEA) a dopamine D4 receptor ligand. In order to synthesize n.c.a. (±)-3-(4-hydroxy-4-(4-[18F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the 18F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic 18F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([18F]fluoroaryloxy)alkylamines via n.c.a. 4-[18F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [18F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[18F]fluorobenzene proved advantageous in comparison to direct use of 4-[18]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [18F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[18F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[18F]fluorobenzene, [18F]FPTEA was obtained by reaction with 2-(4-tolyloxy)ethylamine in radiochemical yields of about 25-30% in ethanol or 2-butanone as solvent with a synthesis

  3. [18F]-FDG coincidence imaging in patients with increased CA 15-3 levels during follow-up for breast cancer

    This study evaluated the usefulness of 18-Fluoro-Deoxy-Glucose imaging performed with a Coincidence Detection Emission Tomography camera ([18F]-FDG-CDET) in the detection of breast cancer recurrence. 27 patients with increasing CA 15-3 levels during follow-up were included in this study. 18FDG imaging was performed with a CDET camera in all patients. [18F]-FDG-CDET findings were compared with other imaging modalities results. Recurrence was confirmed in 25/27 patients and included 5 patients with local-regional recurrences and one with local-regional and liver metastasis, 10 with visceral metastases and 9 patients with bone metastases. No recurrence was confirmed in the remaining 2 patients during a 2 years follow-up. The overall sensitivity of [18F]-FDG-CDET and other imaging modalities was similar (88% and 80% respectively). [18]-FDG-CDET and abdominal CT had similar sensitivity (66% and 63% respectively) in the diagnosis of liver metastases. In detection of bone metastases, the sensitivity of [18F]-FDG-CDET and bone scintigraphy was similar. In patients with local-regional recurrences, [18F]-FDG-CDET detected 6/6 recurrences and other imaging modalities 4/6. In this study, [18F]-FDG-TEDC had similar performance than a strategy combining several imaging modalities for metastases and a better performance for local-regional recurrence detection. (author)

  4. Comparative study of 18F-DOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors

    Jacob, Mattakarottu J; Pandit, Aniruddha G; Jora, Charu; Mudalsha, Ravina; Sharma, Amit; Pathak, Harish C

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT. Materials and Methods: Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with F18-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with F18-FDG. Conclusion: 18F-FDOPA PET is more reliable than F18-FDG and 13N-Ammonia PET for evaluating brain tumors. PMID:23326065

  5. Clearance of the high intestinal {sup 18}F-FDG uptake associated with metformin after stopping the drug

    Oezuelker, Tamer [Okmeydani Training and Research Hospital, Department of Nuclear Medicine, istanbul (Turkey); Daruessafaka Mah. Gazeteciler Sitesi, Maslak, Istanbul (Turkey); Oezuelker, Filiz; Oezpacaci, Tevfik [Okmeydani Training and Research Hospital, Department of Nuclear Medicine, istanbul (Turkey); Mert, Meral [Okmeydani Training and Research Hospital, Department of Internal Medicine, istanbul (Turkey)

    2010-05-15

    This study was done to determine whether interruption of metformin before {sup 18}F-FDG PET/CT imaging could prevent the increased {sup 18}F-FDG uptake in the intestine caused by this drug. Included in the study were 41 patients with known type 2 diabetes mellitus who were referred to our department for evaluation of various neoplastic diseases. Patients underwent two {sup 18}F-FDG PET/CT scans, the first while they were on metformin and the second after they had stopped metformin. They stopped metformin and did not take any other oral antidiabetic medication starting 3 days before the second study and their blood glucose level was regulated with insulin when necessary to keep it within the range 5.55-8.33 mmol/l. FDG uptake was graded visually according to a four-point scale and semiquantitatively by recording the maximum standardized uptake value (SUVmax) in different bowel segments. A paired-samples t-test method was used to determine whether there was a significant difference between SUVmax measurements and visual analysis scores of the metabolic activity of the bowel in the PET/CT scans before and after stopping metformin. Diffuse and intense {sup 18}F-FDG uptake was observed in bowel segments of patients, and the activity in the colon was significantly decreased both visually and semiquantitatively in PET/CT scans performed after patients stopped metformin (p<0.05). There was a statistically significant decrease in activity in the small intestine on visual analysis (p<0.05), but semiquantitative measurements did not show a significant decrease in the SUVmax values in the duodenum or jejunum (p>0.05). Metformin causes an increase in {sup 18}F-FDG uptake in the bowel and stopping metformin before PET/CT study significantly decreased this unwanted uptake, especially in the colon, facilitating the interpretation of images obtained from the abdomen and preventing the obliteration of lesions. (orig.)

  6. Acute and subacute toxicity of 18F-FDG

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the 18F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  7. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis

    Gormsen, Lars C; Haraldsen, Ate; Kramer, Stine;

    2016-01-01

    BACKGROUND: Cardiac sarcoidosis (CS) is a potentially fatal condition lacking a single test with acceptable diagnostic accuracy. (18)F-FDG PET/CT has emerged as a promising imaging modality, but is challenged by physiological myocardial glucose uptake. An alternative tracer, (68)Ga-DOTANOC, binds...

  8. Can brown fat uptake of 18F-FDG be reduced by beta-blockers?

    -Ge external pin sources. Results: All patients showed absence of uptake of FDG in BAT, post propranolol. Discussion: Intense FDG uptake in BAT can lead to false positive FDG PET findings. BAT is known to exhibit increased glucose uptake when the sympathetic nervous system is activated by cold stimulation. BAT has rich adrenergic innervation. BAT acts as a thermogenic organ by producing heat to maintain body temperature especially in young individuals. BAT requires glucose as a source of adenosine triphosphate (ATP). This ATP is required for fatty acid oxidation, which is the main mechanism for heat production. In this study, we demonstrated that the intense FDG uptake in BAT can be successfully eliminated by giving 40 mg of propranolol orally 30 minutes prior to the 18-F FDG injection. Propranolol is a non- selective beta-adrenergic receptor blocking agent. It has no other autonomic nervous system activity. It is rapidly and completely absorbed from the gastrointestinal tract and undergoes extensive first-pass elimination due to its high hepatic clearance. Conclusion: Propranolol reduces the uptake of 18F FDG in BAT and thus improves the accuracy of PET imaging. (author)

  9. 3D tumour spheroids as a model to assess the suitability of [18F]FDG-PET as an early indicator of response to PI3K inhibition

    Background: [18F] Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET) is widely used to monitor response to therapy in the clinic and has, more recently, been proposed as an early marker of long term response. This relies on the assumption that a change in glucose consumption parallels a reduction in viability and long term growth potential. However, cells may utilise substrates other than glucose and as many therapeutics interfere with glucose metabolism directly, it is entirely plausible that a positive [18F]FDG-PET response may be unrelated to long term growth. Furthermore, changes in metabolism and proliferation may take place on different temporal scales, thus restricting the time window in which [18F]FDG-PET is predictive. The PI3K oncogenic signalling pathway is a master regulator of multiple cellular processes including glucose metabolism, proliferation and cell survival. Inhibition of PI3K has been shown to reduce [18F]FDG uptake in several tumour types but the relative influence of this pathway on glucose metabolism and proliferation is not fully established. Aim: We proposed to (i) assess the suitability of [18F]FDG as a tracer for measuring response to PI3K inhibition and (ii) determine the optimum imaging schedule, in vitro. We used multicellular tumour spheroids, an excellent 3D in vitro model of avascular tumours, to investigate the effects of the PI3K inhibitors, NVP-BKM120 and NVP-BEZ235, on [18F]FDG uptake and its relation to 3D growth. Methods: Spheroids were prepared from two cell lines with a constitutively active PI3K/Akt pathway, EMT6 (highly proliferative mouse mammary) and FaDu (moderately proliferate human nasopharyngeal). Treatment consisted of a 24 h exposure to either inhibitor, and growth was monitored over the following 7 days. To mimic potential imaging regimens with [18F]FDG-PET, average [18F]FDG uptake per viable cell was measured (a) directly following the 24 h exposure, (b) following an additional 24 h recovery period

  10. The influence of tumor oxygenation on 18F-FDG (Fluorine-18 Deoxyglucose) uptake: A mouse study using positron emission tomography (PET)

    This study investigated whether changing a tumor's oxygenation would alter tumor metabolism, and thus uptake of 18F-FDG (fluorine-18 deoxyglucose), a marker for glucose metabolism using positron emission tomography (PET). Tumor-bearing mice (squamous cell carcinoma) maintained at 37°C were studied while breathing either normal air or carbogen (95% O2, 5% CO2), known to significantly oxygenate tumors. Tumor activity was measured within an automatically determined volume of interest (VOI). Activity was corrected for the arterial input function as estimated from image and blood-derived data. Tumor FDG uptake was initially evaluated for tumor-bearing animals breathing only air (2 animals) or only carbogen (2 animals). Subsequently, 5 animals were studied using two sequential 18F-FDG injections administered to the same tumor-bearing mouse, 60 min apart; the first injection on one gas (air or carbogen) and the second on the other gas. When examining the entire tumor VOI, there was no significant difference of 18F-FDG uptake between mice breathing either air or carbogen (i.e. air/carbogen ratio near unity). However, when only the highest 18F-FDG uptake regions of the tumor were considered (small VOIs), there was a modest (21%), but significant increase in the air/carbogen ratio suggesting that in these potentially most hypoxic regions of the tumor, 18F-FDG uptake and hence glucose metabolism, may be reduced by increasing tumor oxygenation. Tumor 18F-FDG uptake may be reduced by increases in tumor oxygenation and thus may provide a means to further enhance 18F-FDG functional imaging

  11. Metabolic characteristics distinguishing intrahepatic cholangiocarcinoma: a negative pilot study of (18)F-fluorocholine PET/CT clarified by transcriptomic analysis.

    Kwee, Sandi A; Okimoto, Gordon S; Chan, Owen Tm; Tiirikainen, Maarit; Wong, Linda L

    2016-01-01

    PET using fluorine-18 fluorocholine ((18)F-fluorocholine) may detect malignancies that involve altered choline metabolism. While (18)F-fluorocholine PET/CT has shown greater sensitivity for detecting hepatocellular carcinoma (HCC) than (18)F-fluoro-D-deoxyglucose (FDG) PET/CT, it is not known whether it can also detect intrahepatic cholangiocarcinoma (ICC), a less common form of primary liver cancer. Clinical, radiographic, and histopathologic data from 5 patients with ICC and 23 patients with HCC from a diagnostic trial of liver (18)F-fluorocholine PET/CT imaging were analyzed to preliminarily evaluate (18)F-fluorocholine PET/CT for ICC. Imaging was correlated with whole-genome expression profiling to identify molecular pathways associated with tumor phenotypes. On PET/CT, all ICC tumors demonstrated low (18)F-fluorocholine uptake with a significantly lower tumor to mean background uptake ratio than HCC tumors (0.69 vs. 1.64, p < 0.0001), but no corresponding significant difference in liver parenchyma uptake of (18)F-fluorocholine between ICC and HCC patients (8.0 vs. 7.7, p = 0.74). Two ICC patients demonstrated increased tumor metabolism on FDG PET/CT, while immunohistochemical analysis of ICC tumors revealed overexpression of glucose transporter 1 (GLUT-1) and hexokinase indicating a hyper-glycolytic phenotype. Gene expression analysis revealed down-regulation of farnesoid-X-receptor and other lipid pathways in ICC relative to HCC, and up-regulation of glycolytic pathways and GLUT-1 by HIF1α. These results imply limited utility of (18)F-fluorocholine in ICC, however, significant metabolic differences between ICC, HCC, and parenchymal liver tissue may still provide clues about the underlying liver pathology. Gene and protein expression analysis support hyperglycolysis as a more dominant metabolic trait of ICC. PMID:27069767

  12. Metabolic characteristics distinguishing intrahepatic cholangiocarcinoma: a negative pilot study of 18F-fluorocholine PET/CT clarified by transcriptomic analysis

    Kwee, Sandi A; Okimoto, Gordon S; Chan, Owen TM; Tiirikainen, Maarit; Wong, Linda L

    2016-01-01

    PET using fluorine-18 fluorocholine (18F-fluorocholine) may detect malignancies that involve altered choline metabolism. While 18F-fluorocholine PET/CT has shown greater sensitivity for detecting hepatocellular carcinoma (HCC) than 18F-fluoro-D-deoxyglucose (FDG) PET/CT, it is not known whether it can also detect intrahepatic cholangiocarcinoma (ICC), a less common form of primary liver cancer. Clinical, radiographic, and histopathologic data from 5 patients with ICC and 23 patients with HCC from a diagnostic trial of liver 18F-fluorocholine PET/CT imaging were analyzed to preliminarily evaluate 18F-fluorocholine PET/CT for ICC. Imaging was correlated with whole-genome expression profiling to identify molecular pathways associated with tumor phenotypes. On PET/CT, all ICC tumors demonstrated low 18F-fluorocholine uptake with a significantly lower tumor to mean background uptake ratio than HCC tumors (0.69 vs. 1.64, p < 0.0001), but no corresponding significant difference in liver parenchyma uptake of 18F-fluorocholine between ICC and HCC patients (8.0 vs. 7.7, p = 0.74). Two ICC patients demonstrated increased tumor metabolism on FDG PET/CT, while immunohistochemical analysis of ICC tumors revealed overexpression of glucose transporter 1 (GLUT-1) and hexokinase indicating a hyper-glycolytic phenotype. Gene expression analysis revealed down-regulation of farnesoid-X-receptor and other lipid pathways in ICC relative to HCC, and up-regulation of glycolytic pathways and GLUT-1 by HIF1α. These results imply limited utility of 18F-fluorocholine in ICC, however, significant metabolic differences between ICC, HCC, and parenchymal liver tissue may still provide clues about the underlying liver pathology. Gene and protein expression analysis support hyperglycolysis as a more dominant metabolic trait of ICC. PMID:27069767

  13. Relations between pathological markers and radioiodine can and 18F-FDG PET/CT findings in papillary thyroid cancer patients with recurrent cervical nodal metastases

    The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and 18F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases. A total of 46 PTC patients who had undergone a radioiodine scan and/or 18F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent 18F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and 18F-FDG PET findings were evaluated. Of the 38 patients who underwent 18F-FDG PET/CT, all patients with weak Tg expression had positive 18F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive 18F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake. The 18F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A

  14. Relations between pathological markers and radioiodine can and {sup 18}F-FDG PET/CT findings in papillary thyroid cancer patients with recurrent cervical nodal metastases

    Lee, Jeong Won [Dept. of Nuclear Medicine, Catholic Kwandong University International St. Mary' s Hospital, Seoul (Korea, Republic of); Min, Hye Sook [Dept. of athology, Seoul National University Hospital, Seoul (Korea, Republic of); Lee, Sang Mi [Dept. of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of); Kwon, Hyun Woo; Chung, June Key [Dept. of Nuclear Medicine,Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and {sup 18}F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases. A total of 46 PTC patients who had undergone a radioiodine scan and/or {sup 18}F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent {sup 18}F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and {sup 18}F-FDG PET findings were evaluated. Of the 38 patients who underwent {sup 18}F-FDG PET/CT, all patients with weak Tg expression had positive {sup 18}F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive {sup 18}F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake. The {sup 18}F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A.

  15. The evaluation of breast cancer curative effect and prognosis in 18F-FDG PET/CT

    Objective: To evaluate the value of using 18F-Fluro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in followup studies of breast cancer patients which have been given to comprehensive treatment. Methods: Measuring the standardized uptake value (SUV) of 18F-FDG PET/CT by a retrospective research breast cancer patients in PET Center during November, 2003 to December, 2010 and following up. And analyzing the prognosis of the patients. Results: 114 patients of breast cancer which was confirmed by pathology have been screened out. In which 64 patients showed negative results when having 18F-FDG PET/CT scan, while in other 50 cases of recurrence, residual or metastasis, showed positive results. Average standardized uptake value (SUVave) of the positive results was ranging from 1.0∼11.2 (3.9±1.9), and maximum standardized uptake value (SUVmax) was from 1.1∼ 16.2 (5.0±2.8). The sensitivity, specificity and accuracy of 18F-FDG PET/CT were 96.0%, 100% and 98.5% in diagnosis of breast cancer, while in traditional imaging were 81.8%, 77.6% and 72.9%. By the time of following up, 33 out of 50 positive patients had undergone certain therapies of breast cancer. 17 positive patients were without any therapy. Spearman rank correlation analysis results showed the positive patients in PET/CT scanning with higher maximum standardized uptake value the worse the prognosis. Fisher exact test showed the positive patients with or without treatment prognosis had significant difference. Other 43 patients had no evidence of disease/recurrence or new metastases of breast cancer. 28 of them had undergone certain therapies of breast cancer, while 36 hadn't. Fisher exact test showed the positive patients with or without treatment prognosis hadn't significant difference. Conclusion: 18F-FDG PET/CT scan can find recurrence or metastases of breast cancer at the early stage. It will be a valid way to project prognosis of the patient. And 18F-FDG PET/CT scan can

  16. Background Intestinal 18F-FDG Uptake Is Related to Serum Lipid Profile and Obesity in Breast Cancer Patients.

    Hai-Jeon Yoon

    Full Text Available This study investigated the relationships between background intestinal uptake on 18F-FDG PET and cardio-metabolic risk (CMR factors.A total of 326 female patients that underwent 18F-FDG PET to determine the initial stage of breast cancer were enrolled. None of the patients had history of diabetes or hypertension. The background intestinal uptake on PET was visually graded (low vs. high uptake group and quantitatively measured using the maximal standardized uptake value (SUVmax. SUVmax of 7 bowel segments (duodenum, jejunum, ileum, cecum, hepatic flexure, splenic flexure, and descending colon-sigmoid junction were averaged for the total bowel (TB SUVmax. Age, body mass index (BMI, fasting blood glucose level (BST, triglyceride (TG, cholesterol, high density lipoprotein (HDL, and low density lipoprotein (LDL were the considered CMR factors. The relationships between background intestinal 18F-FDG uptake on PET and diverse CMR factors were analyzed.The visual grades based on background intestinal 18F-FDG uptake classified 100 (30.7% patients into the low uptake group, while 226 (69.3% were classified into the high uptake group. Among CMR factors, age (p = 0.004, BMI (p<0.001, and TG (p<0.001 were significantly different according to visual grade of background intestinal 18F-FDG uptake. Quantitative TB SUVmax showed significant positive correlation with age (r = 0.203, p<0.001, BMI (r = 0.373, p<0.001, TG (r = 0.338, p<0.001, cholesterol (r = 0.148, p = 0.008, and LDL (r = 0.143, p = 0.024 and significant negative correlation with HDL (r = -0.147, p = 0.022. Multivariate analysis indicated that BMI and TG were independent factors in both visually graded background intestinal 18F-FDG uptake (p = 0.027 and p = 0.023, respectively and quantitatively measured TB SUVmax (p = 0.006 and p = 0.004, respectively.Increased background intestinal 18F-FDG uptake on PET may suggest alteration of lipid metabolism and risk of cardio-metabolic disease in non

  17. Synthesis of 2'-deoxy-2'-[{sup 18}F]fluoro-5-bromo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FBAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-chloro-1-{beta}-D-arabinofuranosyl-uracil ([{sup 18}F]-FCAU), and their biological evaluation as markers for gene expression

    Alauddin, Mian M. E-mail: alauddin@usc.edu; Shahinian, Antranic; Park, Ryan; Tohme, Michel; Fissekis, John D.; Conti, Peter S

    2004-05-01

    [{sup 18}F]-FBAU and [{sup 18}F]-FCAU have been synthesized and evaluated in vivo as markers for HSV1-tk gene expression. At 2 hours, uptake of [{sup 18}F]-FBAU and [{sup 18}F]-FCAU in HSV1-tk-positive tumors was 7.9-fold and 6.0-fold higher than the control tumors, respectively. Micro-PET images also showed very high uptake in HSV-tk tumors. Compared to [{sup 14}C]-FMAU, total uptake of [{sup 18}F]-FBAU and [{sup 18}F]-FCAU was similar in tk-positive cells, but the uptake ratio (tk+/wild) was higher. [{sup 18}F]-FBAU and [{sup 18}F]-FCAU appear to be potential PET imaging agents for gene expression.

  18. The optimization of 18F-nucleophilic fluorination reaction and its application in synthesis of VMAT2 imaging tracer: [18F]AV-133

    Objective: The nucleophilic introduction of n.c.a. [18F]F- into alkanes by nucleophilic reaction is the main method of preparing 18F-labelled radiopharmaceuticals, and the efficient and rapid reaction is important in 18F-labelled radiopharmaceuticals. Method: Using 2-(3-substitute propoxy)naphthalene as model compound, the optimal reaction condition was achieved by comparing the different [18F]fluorination condition: 1)different leaving groups (-OTs, -I, -Br and -Cl), 2) different [18F]fluorination catalysts (Kryptofix222/K2CO3 and TBAHCO3), 3) different reaction solvent (ACN, DMSO and DMF), 4) [18F]fluorination temperature (40, 50 and 60 degree C) and 5) reaction time. The radiochemical yields were analyzed by TLC and HPLC. VMAT2 imaging tracer [18F]AV-133 was synthesized under the optimal conditions. Results: From the experiment results, the reation activity was the highest when using -OTs as the leaving group, followed by -I and -Br, -Clunder the [18F]fluorination condition of using K222/K2CO3 as catalyst and ACN as solvent. And also, the radiochemical yield raised as the reaction time and temperature increased. The higher temperature, the shorter time to reach the equilibrium. When changing the solvent from ACN to DMSO, the radiochemical yields were increased. On the contrary, the radiochemical yields were decreasing by using DMF. Comparing the catalyst K222/K2CO3 with TBAHCO3, the [18F] fluorination of -OTs gave a higher radiochemical yield in the presence of K222/K2CO3. So the optimized [18F]fluorination reaction condition was that choosing -OTs as the leaving group, the [18F]fluorination reaction was efficient and gave higher radiochemical yield catalyzed by K222/K2CO3 in DMSO at high temperature. [18F]fluorination of AV-244 was found to provide the VMAT2 imaging tracer [18F]AV-133 in 80 ± 2% radiochemical yield after reaction at 120 degree C for 3 min under optimized conditions. Conclusion: We have described an optimized condition of nucleophilic [18F

  19. C-(4-[18F]fluorophenyl)-N-phenyl nitrone: A novel 18F-labeled building block for metal free [3+2]cycloaddition

    Radiofluorination via [3+2]-nitrone-alkene cycloaddition was studied using the model reaction between 18F-labeled C-(4-fluorophenyl)-N-phenyl nitrone ([18F]1) and substituted maleimides 2a–c. [18F]1 was prepared in RCY of 73.6±5.8% and radiochemical purity of >95%. Cycloaddition of [18F]1 to 2a in toluene at 80 °C and in EtOH at 110 °C gave the respective isoxazolidine [18F]5a in >80% RCY at 10 min reaction time. Reaction between [18F]1 and 2b, c also went smoothly to afford the respective cycloaddition products in high radiochemical yields. - Highlights: ► [2+3]-Nitrone-alkene metal-free cycloaddition for radiolabelling. ► Optimized radiosynthesis of C-(4-[18F]fluorophenyl)-N-phenyl nitrone ([18F]1). ► Fast and high-yielding cycloaddition of [18F]1 to model maleimides.

  20. Manufacture and application of a microfluidic chip-based 18F microreactor

    Objective: To develop a polydimethylsiloxane (PDMS) microfluidic chip-based 18F microreactor for the preparation of 18F-labeled probes. Methods: The 18F microreactor was composed of PDMS microfluidic chip and customized glass microvessel integrating with stainless capillary tube (D 0.6 mm) as heater/cooler. PDMS chips were fabricated by silk-screen printing technology,a traditional and easily accessible process. 18F-FDG and 18F-fluoroacetate (FAC) were synthesized using the 18F microreactor. TLC was applied to measure the 18F-labeling yield and the radiochemical purity of 18F-FDG and 18F-FAC. Results: The size of PDMS chip was 40.0 mm (l)×30.0 mm (w)×6.0 mm(h) and the liquid/gas inside channel was 0.3 mm (w)×50.0 μm (h). The customized glass microvessel was about 4.0 mm (D) ×30.0 mm (h) with 200 μl of reaction volume. The capillary tube which wrapped around the microvessel functioned as a heater when electric current was provided, while as a cooler when compressed air went through. The integrated 18F microreactor with a total size of 40.0 mm (l) ×30.0 mm (w) ×15.0 mm (h) was successfully used to prepare 18F-FDG and 18F-FAC, whose radiochemical purity were both higher than 96% and 18F-labeling yield was 92.5% and 90.0% respectively in the first fluorination step. Conclusions: A PDMS microfluidic chip-based 18F microreactor is developed and successfully applied to prepare 18F-FDG and 18F-FAC. It has the dual advantages of both microfluidic chip and traditional synthesis module and features of high integration, small total size and low consumption of labeling precursor. (authors)

  1. (18)F-FDG PET/CT in a rare case of Stewart-Treves syndrome

    Jensen, Mads Radmer; Friberg, Lars; Karlsmark, Tonny;

    2011-01-01

    The aim of this article is to illustrate the possible applications of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG PET/CT) in chronic extremity lymphedema and its complications.......The aim of this article is to illustrate the possible applications of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG PET/CT) in chronic extremity lymphedema and its complications....

  2. Automated Synthesis of 18F-Fluoropropoxytryptophan for Amino Acid Transporter System Imaging

    I-Hong Shih

    2014-01-01

    Full Text Available Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP to assess tryptophan transporters using an automated synthesizer. Methods. Tosylpropoxytryptophan (Ts-TP was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1 and HPLC (C-18 column, methanol : water = 7 : 3 analyses. In vitro cellular uptake of 18F-FTP and 18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with 18F-FTP and 18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv. Results. Radio-TLC and HPLC analyses of 18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected. Cellular uptake of 18F-FTP and 18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that 18F-FTP had less tumor uptake than 18F-FDG in prostate cancer model. However, 18F-FTP had more uptake than 18F-FDG in small cell lung cancer model. Conclusion. 18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by 18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

  3. Automated production and quality testing of [18F]labeled radiotracers using the BG75 system

    The simplification and automation of clinical PET radiotracer production, from isotope production to quality control, can streamline the current manufacturing workflow and, at the same time minimize the investment needed. In this article we present pre-clinical and clinical results showing the feasibility for manufacture of [18F]fluoride labeled radiotracers such as [18F]FDG, [18F]NaF and [18F]FMISO under automated conditions using the BG75 system. (author)

  4. New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule Generation from the Solid Phase.

    Rodriguez, Erik A; Wang, Ye; Crisp, Jessica L; Vera, David R; Tsien, Roger Y; Ting, Richard

    2016-05-18

    New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin-bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [(18)F]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [(18)F]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases. PMID:27064381

  5. Acute and subacute toxicity of {sup 18F}-FDG

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A., E-mail: danielle_2705@hotmail.com, E-mail: jaossoj@yahoo.com.br, E-mail: ngsilva@ipen.br, E-mail: apaulasp2008@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the {sup 18}F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  6. Statistical Analysis Of Tank 18F Floor Sample Results

    Representative sampling has been completed for characterization of the residual material on the floor of Tank 18F as per the statistical sampling plan developed by Shine (1). Samples from eight locations have been obtained from the tank floor and two of the samples were archived as a contingency. Six samples, referred to in this report as the current scrape samples, have been submitted to and analyzed by SRNL (2). This report contains the statistical analysis of the floor sample analytical results to determine if further data are needed to reduce uncertainty. Included are comparisons with the prior Mantis samples results (3) to determine if they can be pooled with the current scrape samples to estimate the upper 95% confidence limits (UCL95%) for concentration. Statistical analysis revealed that the Mantis and current scrape sample results are not compatible. Therefore, the Mantis sample results were not used to support the quantification of analytes in the residual material. Significant spatial variability among the current sample results was not found. Constituent concentrations were similar between the North and South hemispheres as well as between the inner and outer regions of the tank floor. The current scrape sample results from all six samples fall within their 3-sigma limits. In view of the results from numerous statistical tests, the data were pooled from all six current scrape samples. As such, an adequate sample size was provided for quantification of the residual material on the floor of Tank 18F. The uncertainty is quantified in this report by an upper 95% confidence limit (UCL95%) on each analyte concentration. The uncertainty in analyte concentration was calculated as a function of the number of samples, the average, and the standard deviation of the analytical results. The UCL95% was based entirely on the six current scrape sample results (each averaged across three analytical determinations).

  7. Diagnostic value of 18F-FDG PET and 11C-PIB PET on early stage posterior cortical atrophy

    Shuai LIU

    2015-08-01

    Full Text Available Background  Posterior cortical atrophy (PCA is a kind of progressive neurodegenerative disease with cortical visual impairment as the first symptom. Because of rare clinical incidence, early onset age, special clinical symptoms and unobvious MRI abnormality, the definitive diagnosis of PCA is difficult. This study used 18F-fluoro-2-deoxy-D-glucose (18F-FDG PET and 11C-Pittsburgh compound B (11C-PIB PET for PCA patients with unobvious MRI abnormality, so as to discuss the value of PET in the early diagnosis of PCA.  Methods  Five patients diagnosed as PCA in our hospital between April 2012 and March 2015 were enrolled in this study. Cognitive function was measured by Mini-Mental State Examination (MMSE, Montreal Cognitive Assessment (MoCA, Activities of Daily Living (ADL and Clock Drawing Test (CDT. Brain MRI, 18F-FDG PET and 11C-PIB PET were performed to analyze glucose metabolism and perfusion of posterior cortex.  Results Neuropsychological tests revealed that the ability of writing, calculating, visuospatial and executive function of all these patients were impaired. Color vision tests showed abnormal results. MRI showed that the posterior atrophy (PA scores were 0-2 (average 1 on the left side and 0-1 (average 0.80 on the right side. The medial temporal atrophy (MTA scores were 1-3 (average 1.80 on the left side and 1-4 (average 2 on the right side. The ventricular enlargement (VE scores were 1-2 (average 1.80 on the left side and 1-2 (average 1.60 on the right side. 18F-FDG PET showed glucose metabolism decreased obviously on bilateral temporo-parieto-occipital cortex, precuneus and cingulate gyrus, and slightly on frontal lobes and subcortical structure. 11C-PIB PET showed radioactive 11C-PIB deposition on bilateral frontal, temporal, parietal and occipital cortex, and the outline of cerebellar cortex was clear.  Conclusions  For PCA patients whose parietal and occipital cortical atrophy is not obvious on MRI, 18F-FDG PET

  8. Radiosynthesis of [18F]fluorophenyl-L-amino acids by isotopic exchange on carbonyl-activated precursors

    Castillo Meleán, J.

    2011-01-01

    ABSTRACT Aromatic [18F]fluoroamino acids have earlier been developed as promising probes for diagnostics using PET. However, a wider use of these radiofluorinated compounds has been limited due to radiosynthetic constraints. The work here presents an amenable three-step radiosynthesis pathway for the preparation of 2-[18F]fluoro-L-phenylalanine (2-[18F]Fphe), 2-[18F]fluoro-L-tyrosine (2-[18F]Ftyr), 6-[18F]fuoro-L-m-tyrosine (6-[18F]Fmtyr) and 6-[18F]fluoro-L-DOPA (6-[18F]FDOPA). For this, ...

  9. A quantitative comparison of gross tumour volumes delineated on [18F]-FDG PET-CT scan and CECT scan in head and neck cancers

    Venkada, Manickam G; Rawat, Sheh; Choudhury, PS; T. Rajesh; Rao, SA; Khullar, Pooja; Kakria, Anjali

    2012-01-01

    Purpose: To compare quantitatively Gross tumor volume (GTV), both primary and nodal areas of head and neck cancers, delineated on [18F]-2fluoro, 2deoxy d-glucose-positron emission tomography/computed tomography ([18F]-FDG-PET-CT) scan to those delineated on Contrast-enhanced CT scan (CECT scan). Methods: A total of 26 consecutive patients with squamous cell cancers of head and neck were included in this study. The primary sites were oropharynx (n = 7), hypopharynx (n = 6), paranasal sinus (n ...

  10. Effect of Gemcitabine in the Uptake of 18F-FDG Non-small-cell on Human Lung Cancer Cell A549%吉西他滨对人非小细胞肺癌A549细胞摄取18F-FDG影响的研究

    邹惠峰; 邓胜明; 章斌; 吴翼伟

    2011-01-01

    目的 探讨测定人非小细胞肺癌A549细胞的18F-FDG细胞结合率方法及用吉西他滨化疗后对A549细胞摄取18FFDG的影响.方法 在不同条件下测定A549细胞的18F-FDG细胞结合率,细胞浓度5×104~1×107/瓶;18F-FDG放射性活度1.85~29.6KBq;反应时间20~120min;葡萄糖浓度0~11.1mmol/L.MTT测定加入不同剂量0~120mmol/L吉西他滨24h后细胞抑制率.测定加入不同剂量0~120mmol/L吉西他滨24h后18F-FDG细胞结合率.结果 18F-FDG细胞结合率随细胞数量、反应时间的增加而增高,随葡萄糖浓度的增高而降低,与18F-FDG放射性活度无关;加入不同剂量吉西他滨后,细胞结合率随剂量增加而下降,两者呈负相关(r=-0.78,P<0.01).结论吉西他滨作用24h后引起人非小细胞肺癌A549细胞 18F-FDG细胞结合率下降,可用18F-FDG显像早期观测吉西他滨对人非小细胞肺癌疗效.%Objective To optimize the measurement of 18F-FDG uptake rates of non-small-cell lung cancer cell A549 and investigate the effect after administrated with Gemcitabine. Methods To detect 18F-FDG uptake rates of non-small-cell lung cancer A549 cells in different conditions:cell density ranges from 5 × 104 to 1 × 107per flask,radioactivity of 18F-FDG from 1.85 to 29.6KBq,incubating time from 20 to 120 minutes,glucose concentration from 0 to 11.1mmol/L.24 hours after administrated with Gemcitabine(0 ~ 120mmol/L),inhibition ratios and 18F-FDG uptake rates of the A549 cells were detected. Results On certain conditions,18F-FDG uptake rates of A549 cells increased as the cell number and incubating time grew,but decreased while glucose concentration raised,irrelative with radioactivity of 18F-FDG.18F-FDG uptake rates of A549 cells decreased with the concentration of Gemcitabine increasing,which presented negative correlation(r=-0.78,P<0.01).Conclusions 18F-FDG uptake rates of non-small-cell lung cancer A549 cells decreased 24 hours after treated with Gemcitabine

  11. [18F]FLT and [18F]FDG PET for non-invasive treatment monitoring of the nicotinamide phosphoribosyltransferase inhibitor APO866 in human xenografts

    Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram; Björkling, Fredrik;

    2013-01-01

    APO866 is a new anti-tumor compound inhibiting nicotinamide phosphoribosyltransferase (NAMPT). APO866 has an anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell pr...

  12. Direct comparison of [18F]MH.MZ and [18F]altanserin for 5-HT2A receptor imaging with PET

    Hansen, Hanne Demant; Ettrup, Anders; Herth, Matthias Manfred;

    2013-01-01

    Imaging the cerebral serotonin 2A (5-HT(2A) ) receptors with positron emission tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and [(18) F]altanserin. Recently, the MDL 100907 analogue [(18) F]MH.MZ was developed combining the selectivity profile of MDL 100907 and the favo....... Synapse, 2013. © 2013 Wiley Periodicals, Inc....

  13. Assessment of Tumor Response to Therapy in Lymphoma Using 18F-FDG PET: Diagnostic Performance of 18F-FDG PET and Interval Likelihood Ratio

    In this paper, the authors intended to summarize briefly the features of lymphoma with regard to 18F-FDG PET for assessment of tumor response to therapy, to describe why assessment of treatment response should be performed, to review what method so far has been used in monitoring treatment response, to discuss what limitations of morphologic imaging criteria for assessing tumor response are, in compared with 18F-FDG PET, and to introduce recently proposed criteria for assessing tumor response in malignant lymphoma. And also the authors emphasize the need to understand the characteristics of diagnostic performance of 18F-FDG PET in several clinical settings in order to interpret 18F-FDG PET results appropriately, and to encourage the use of interval likelihood ratio to enhance clinical implications of test results which, in turns, allows referring physicians to understand the meaning of interpretation with easy. Until recently, treatment response has been assessed according to the morphologic criteria. Metabolic imaging with 18F-FDG PET was adopted to have important role for treatment assessment in IWC+PET criteria proposed recently by IHP. To accomplish this role, we should perform and interpret 18F-FDG PET according to IWC+PET criteria. It is important for referring physicians to understand the various limitations of 18F-FDG PET and pitfalls in PET interpretation, and to understand that clinical information are needed by nuclear medicine physicians to optimize the interpretation of 18F-FDG PET

  14. Post-target produced [18F]F2 in the production of PET radiopharmaceuticals

    Electrophilic radiofluorination was successfully carried out in the early years of PET radiochemistry due to its ease and fast reaction speed. However, at the present, the use of electrophilic methods is limited due to low specific activity (SA). Post-target produced [18F]F2 has significantly higher SA compared to other electrophilic approaches, and it has been used in the production of clinical PET radiopharmaceuticals at the Turku PET Centre for years. Here, we summarize the synthesis and use of these radiopharmaceuticals, namely [18F]FDOPA, [18F] CFT, [18F]EF5 and [18F]FBPA.

  15. HPLC法分析18F-FDG放化纯度

    2001-01-01

    采用85%的乙腈作流动相,高效糖柱作分离柱,HPLC法分析18F-FDG的放化纯度.在该条件下,18F-的参考保留时间为6.50min,18F-FDG为9.00min.与同一样品的TLC分析比较,HPLC分析18F-FDG时间短、灵敏度高.因此采用HPLC分析18F-FDG的放化纯度优于TLC.

  16. Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma

    Despite multiple advances in cancer therapies, patients with glioblastoma (GBM) still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a reliable method to map hypoxia in preclinical human models may contribute to the discovery and translation of future and more targeted therapies. The aim of this study was to compare the hypoxic status of two commonly used human ortho-topic glioma models (U87 and U251) developed in rats and studied by noninvasive hypoxia imaging with 3-[18F] fluoro-1-(2-nitro-1-imidazolyl)-2-propanol-micro-positron emission tomography ([18F]-FMISO-μPET). In parallel, because of the relationships between angiogenesis and hypoxia, we used magnetic resonance imaging (MRI), histology, and immunohistochemistry to characterize the tumoral vasculature. Although all tumors were detectable in T2-weighted MRI and 2-deoxy-2-[18F]fluoro-D-glucose-mu PET, only the U251 model exhibited [18]-FMISO uptake. Additionally, the U251 tumors were less densely vascularized than U87 tumors. Our study demonstrates the benefits of noninvasive imaging of hypoxia in preclinical models to define the most reliable one for translation of future therapies to clinic based on the importance of intratumoral oxygen tension for the efficacy of chemotherapy and radiotherapy. (authors)

  17. Preparation and evaluation of ethyl [18F]fluoroacetate as a proradiotracer of [18F]fluoroacetate for the measurement of glial metabolism by PET

    Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [18F]fluoroacetate ([18F]EFA), which is [18F]fluoroacetate ([18F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [18F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1-14C]fluoroacetate ([14C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [14C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [14C]EFA was measured. Biodistribution studies of [18F]EFA in ddY mice were carried out and compared with [18F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [18F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [18F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6±3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [14C]EFA was 3.8 times higher than that of sodium [1-14C]fluoroacetate. [14C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [14C]EFA was stable only in primate plasma

  18. Oxidation of substituted 4-fluorobenzaldehydes: an application to the no-carrier-added syntheses of 4-( sup 18 F)fluoroguaiacol and 4-( sup 18 F)fluorocatechol

    Chakraborty, P.K.; Kilbourn, M.R. (Michigan Univ., Ann Arbor, MI (USA). Div. of Nuclear Medicine)

    1991-01-01

    The synthesis of 4-({sup 18}F)fluoroguaiacol (4-({sup 18}F)fluoro-2-methoxyphenol) has been achieved in no-carrier-added form starting from 2-methoxy-4-nitrobenzaldehyde, using nucleophilic aromatic substitution by ({sup 18}F)fluoride followed by Baeyer-Villiger oxidation of the benzaldehyde to the phenol. Demethylation with boron tribromide gave 4-({sup 18}F)fluorocatechol (1,2-dihydroxy-4-({sup 18}F)fluorobenzene) with an overall yield of 18-28% (EOB) in less than 2 h synthesis time. The fluorine-18 labeled intermediates and products were identical to standards of 4-fluoroguaiacol and 4-fluorocatechol prepared by the same methods. This represents a new approach to the synthesis of fluorinated phenols in fluorine-19 and fluorine-18 forms. (author).

  19. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

    Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Zegers, Catharina M.L.; Lieuwes, Natasja G.; Elmpt, Wouter van [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Eriksson, Jonas; Dongen, Guus A.M.S. van [Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam, Amsterdam (Netherlands); Dubois, Ludwig; Lambin, Philippe [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands)

    2015-02-01

    Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put

  20. Increasing feasibility and utility of 18F-FDOPA PET for the management of glioma

    Introduction: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2–5 and 2 years, respectively. PET imaging with 18F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of 18F-DOPA imaging grants utility for a number of clinical applications. Methods: A collection of published work about 18F-FDOPA PET was made and a critical review was discussed and written. Results: A number of research papers have been published demonstrating that in conjunction with MRI, 18F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with 11C-MET, 18F-FLT, 18F-FET and MRI, 18F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making 18F-FDOPA more accessible. Conclusions: According to the available data, 18F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. Advances in knowledge and implication for patient care: 18F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and 18F-FDG PET

  1. A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging

    Huiban, Mickael; Tredwell, Matthew; Mizuta, Satoshi; Wan, Zehong; Zhang, Xiaomin; Collier, Thomas Lee; Gouverneur, Véronique; Passchier, Jan

    2013-11-01

    Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many 18F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with 18F radiochemistry are the short half-life of 18F (<2 h), the use of sub-stoichiometric amounts of 18F, relative to the precursor and other reagents, as well as the limited availability of parent 18F sources of suitable reactivity ([18F]F- and [18F]F2). There is a high-priority demand for general methods allowing access to [18F]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [18F]trifluoromethylation of (hetero)arenes from [18F]fluoride using commercially available reagents and (hetero)aryl iodides. This [18F]CuCF3-based protocol benefits from a large substrate scope and is characterized by its operational simplicity.

  2. A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma

    Danny L. Costantini

    2016-01-01

    Full Text Available We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6±0.6 and 5.0±0.3, versus 18F-FDG SUV 1.9±0.1 and 3.4±0.7, resp., p<0.05. In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of 2.6±0.1 and 2.0±0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned.

  3. Large-Vessel Vasculitis: Interobserver Agreement and Diagnostic Accuracy of 18F-FDG-PET/CT

    K. D. F. Lensen

    2015-01-01

    Full Text Available Introduction. 18F-FDG-PET visualises inflammation. Both atherosclerosis and giant cell arteritis cause vascular inflammation, but distinguishing the two may be difficult. The goal of this study was to assess interobserver agreement and diagnostic accuracy of 18F-FDG-PET for the detection of large artery involvement in giant cell arteritis (GCA. Methods. 31 18F-FDG-PET/CT scans were selected from 2 databases. Four observers assessed vascular wall 18F-FDG uptake, initially without and subsequently with predefined observer criteria (i.e., vascular wall 18F-FDG uptake compared to liver or femoral artery 18F-FDG uptake. External validation was performed by two additional observers. Sensitivity and specificity of 18F-FDG-PET were determined by comparing scan results to a consensus diagnosis. Results. The highest interobserver agreement (kappa: 0.96 in initial study and 0.79 in external validation was observed when vascular wall 18F-FDG uptake higher than liver uptake was used as a diagnostic criterion, although agreement was also good without predefined criteria (kappa: 0.68 and 0.85. Sensitivity and specificity were comparable for these methods. The criterion of vascular wall 18F-FDG uptake equal to liver 18F-FDG uptake had low specificity. Conclusion. Standardization of image assessment for vascular wall 18F-FDG uptake promotes observer agreement, enables comparative studies, and does not appear to result in loss of diagnostic accuracy compared to nonstandardized assessment.

  4. Comparison of the biological effects of {sup 18}F at different intracellular levels

    Kashino, Genro, E-mail: kashino@oita-u.ac.jp [Advanced Molecular Imaging Center, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593 (Japan); Hayashi, Kazutaka; Douhara, Kazumasa [Advanced Molecular Imaging Center, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593 (Japan); Kobashigawa, Shinko; Mori, Hiromu [Department of Radiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593 (Japan)

    2014-11-07

    Highlights: • We estimated the inductions of DNA DSB in cell treated with {sup 18}F-FDG. • We found that inductions of DNA DSB are dependent on accumulation of {sup 18}F in cell. • Accumulation of {sup 18}F in cell may be indispensable for risk estimation of PET. - Abstract: We herein examined the biological effects of cells treated with {sup 18}F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of {sup 18}F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of {sup 18}F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with {sup 18}F-FDG than in those treated with {sup 18}F-HF. The clonogenic survival of cells was significantly lower with {sup 18}F-FDG than with {sup 18}F-HF. We concluded that the efficient accumulation of {sup 18}F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.

  5. Automated electrophilic radiosynthesis of [18F]FBPA using a modified nucleophilic GE TRACERlab FXFDG

    We modified a commercially available synthesis module for nucleophilic [18F]fluorinations (TRACERlabTM FXFDG, GE Healthcare) to enable the reliable synthesis of 2-[18F]fluoro-4-borono-L-phenylalanine ([18F]FBPA) via direct electrophilic substitution of 4-borono-L-phenylalanine with [18F]F2 gas. [18F]FBPA was obtained with a RCY of 8.5±2.0% and a radiochemical purity of 98±1% in a total synthesis time of 72±7 min (n=22). The modified synthesis module might also be useful for the synthesis of other [18F]radiopharmaceuticals via electrophilic substitution reactions while still being suitable for nucleophilic substitution reactions. - Highlights: • Automated synthesis of [18F]FBPA was developed via reaction of BPA with [18F]F2. • [18F]FBPA was obtained with a RCY of 8.5±2.0%. • Nucleophilic synthesis module was adapted for electrophilic [18F]fluorinations. • Modified synthesis module may also enable other electrophilic [18F]fluorinations

  6. Characteristics of [18F] fluorodeoxyglucose uptake in human colon cancer cells

    Cancer tissues are characterized by increased glucose uptake. 18F-fluorodeoxyglucose(FDG), a glucose analogue is used for the diagnosis of cancer in PET studies. This study was aimed to compare the glucose uptake and glucose transporter 1(GLUT1) expression in various human colon cancer cells. We measured FDG uptake by cell retention study and expression of GLUT1 using Western blotting. Human colon cancer cells, SNU-C2A, SNU-C4 and SNU-C5, were used. The cells were incubated with 1μ Ci/ml of FDG in HEPES- buffered saline for one hour. The FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were 16.8±1.36, 12.3±5.55 and 61.0±2.17 cpm/μg of protein, respectively. Dose-response and time-course studies represent that FDG uptake of cancer cells were dose dependent and time dependent. The rate of FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were 0.29±0.03, 0.21±0.09 and 1.07±0.07 cpm/min/μg of protein, respectively. Western blot analysis showed that the GLUT1 expression of SNU-C5 was significantly higher than those of SNU-C2A and SNU-C4. These results represent that FDG uptake into human colon cancer cells are different from each other. In addition, FDG uptake and expression of GLUT1 are closely related in human colon cancer cells

  7. An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate

    Introduction: [18F]Mefway is a serotonin 5-HT1A PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [18F]mefway permits 18F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[18F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[18F]mefway and trans-[18F]mefway to evaluate the properties of cis-[18F]mefway for 5-HT1A PET imaging. Methods: The cis- and trans-[18F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [18F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BPND) using the CB as a reference region. Results: Averaged over the two subjects, BPND values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[18F]mefway and cis-[18F]mefway, respectively. Conclusion: The cis-labeled [18F]mefway tracer has low specific binding throughout the 5-HT1A regions of the brain compared to trans-[18F]mefway, suggesting that the target-to-background binding of cis-[18F]mefway may limit its use for in vivo assessment of 5-HT1A binding.

  8. Using Positron Emission Tomography with [18F]FDG to Predict Tumor Behavior in Experimental Colorectal Cancer

    Bryan M. Burt

    2001-01-01

    Full Text Available This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic 18F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by 18F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

  9. Aortic {sup 18}F-FDG uptake in patients suffering from granulomatosis with polyangiitis

    Kemna, Michael J. [Maastricht University Medical Center, Department of Nephrology and Clinical Immunology, Maastricht (Netherlands); Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Bucerius, Jan [Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); University Hospital RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Drent, Marjolein [Maastricht University, Department of Pharmacology and Toxicology, Maastricht (Netherlands); Voeoe, Stefan [Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Veenman, Martine [Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Paassen, Pieter van [Maastricht University Medical Center, Department of Nephrology and Clinical Immunology, Maastricht (Netherlands); Tervaert, Jan Willem Cohen [Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Sint Franciscus Gasthuis, Noordoever Academy, Rotterdam (Netherlands); Kroonenburgh, Marinus J.P.G. van [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands)

    2015-08-15

    The objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using {sup 18}F-2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT. Aortic inflammation was studied in PET/CT scans obtained from 21 patients with GPA; 14 patients with sarcoidosis were included as disease controls, 7 patients with stage I or II head and neck carcinoma ascertained during routine clinical practice were used as healthy controls (HC) and 5 patients with large vessel vasculitis (LVV) were used as positive controls. Aortic {sup 18}F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUV{sub max}), known as the target to background ratio (mean TBR{sub max}). The mean TBR{sub max} (interquartile range) of the aorta in patients with GPA, sarcoidosis, HC and LVV were 1.75 (1.32-2.05), 1.62 (1.54-1.74), 1.29 (1.22-1.52) and 2.03 (1.67-2.45), respectively. The mean TBR{sub max} was significantly higher in patients suffering from GPA or LVV compared to HC (p < 0.05 and p < 0.005, respectively) and tended to be higher in patients suffering from sarcoidosis, but this did not reach statistical significance (p = 0.098). The mean TBR{sub max} of the most diseased segment was significantly higher compared to HC [1.57 (1.39-1.81)] in LVV patients [2.55 (2.22-2.82), p < 0.005], GPA patients [2.17 (1.89-2.83), p < 0.005] and patients suffering from sarcoidosis [2.04 (1.88-2.20), p < 0.05]. In GPA patients, the mean TBR{sub max} of the aorta was significantly higher in patients with previous renal involvement [2.01 (1.69-2.53)] compared to patients without renal involvement in the past [1.60 (1.51-1.80), p < 0.05]. Interrater reproducibility with a second reader was high (all intraclass correlation coefficients >0.9). Patients suffering from GPA show marked aortic FDG uptake. (orig.)

  10. Local transport of 18F FDG: guidelines and practical aspects

    Full text: Transport of radioactive material in India is governed by Atomic Energy Regulatory Board (AERB) safety code AERB/SC/TR-1 which is based on the International Atomic Energy Agency (IAEA) regulations for the safe transport of radioactive material. The basic requirement for the transport of radioactive material is that the package containing the material shall be designed and prepared in such a way that during the whole process of transport, the radioactive material remains contained to prevent contamination and remains shielded to avoid unacceptable radiation exposure to cargo handlers and public. The types of packages used for the transport of radioactive materials are Excepted, Industrial, Type A, Type B(U) and Type B(M) packages. Type A packages are used for the transport of dispersible radioactive material of moderate activity such as nuclear medicine sources used for diagnostic and therapeutic purposes. Transport of 18F FDG comes under this category. The use of PET-CT in India has grown rapidly over the last few years. Currently, in India, there are around 60 PET-CTs and 15 cyclotrons. Most of these PET-CT facilities are supplied with FDG from off-site cyclotrons. The prime responsibility for ensuring safe transport of 18F FDG lies with the consignor. The consignor needs to ensure that the appropriate packaging is selected for the transport of 18F FDG and the package is prepared, marked and labeled as per the regulations. A material such as Tungsten or lead of appropriate thickness and design is used in packaging. Once the package is prepared as per the prescribed procedures, it can be transported by any mode of transport i.e. by road, rail, sea or air. Transport documents are very important during transport; they include (1) declaration by the consignor, (2) instructions to the carrier, (3) a Transport Emergency Card (TREMCARD) and (4) Instructions in writing to the carrier for emergency measures. In addition to this, one working radiation survey

  11. Reduced myocardial 18F-FDG uptake after calcium channel blocker administration. Initial observation for a potential new method to improve plaque detection

    Physiological glucose uptake by the myocardium may hamper visualization of coronary atherosclerotic plaques in 18F-FDG PET studies. Intracellular myocardial calcium relates to glucose influx. We assessed whether administration of a calcium channel blocker such as verapamil could decrease myocardial 18F-FDG uptake in mice. Experiments were conducted on ten male C57BL/6JOlaHsd mice. The mice were studied by 18F-FDG PET/CT under basal conditions and after a single administration of verapamil injected 1 h prior to 18F-FDG administration at doses of 1 mg/kg (group A, n = 5) and 20 mg/kg (group B, n = 5). PET scanning was started 60 min after injection of 18F-FDG employing a dedicated small-animal PET/CT system (ARGUS-CT). In each mouse, post-verapamil PET images were coregistered with the basal PET images. Volumetric regions of interest (VOI) were drawn on the basal study containing the myocardium of the whole left ventricle and quantitatively compared with the same VOI applied to the post-verapamil scan. The SUVmean was used to express the mean myocardial 18F-FDG uptake. The relative coefficient of variation (RV) between the basal and post-verapamil conditions was calculated. Verapamil administration decreased myocardial 18F-FDG uptake in all animals. The median (range) SUVmean values in group A were 2.6 (1.6-4.1) under basal conditions and 1.7 (1.1-2.9) after verapamil administration (p = 0.043), and in group B were 1.6 (1.3-2.0) under basal conditions and 1.0 (0.9-1.4) after verapamil administration (p = 0.043). The median (range) RV values were -31% (-5%, -50%) in group A, and -37% (-10%, -51%) in group B (p = 0.6). In this animal model there was a significant reduction in 18F-FDG uptake in the myocardium following verapamil administration. This type of intervention could facilitate the definition of coronary atherosclerotic plaque inflammation on 18F-FDG PET scans. (orig.)

  12. Accuracy of 18F-FDG PET/CT for lymph node staging in non-small-cell lung cancers

    LIU Bao-jun; DONG Jing-cheng; XU Chang-qing; ZUO Chuan-tao; LE Jing-jing; GUAN Yi-hui; ZHAO Jun; WU Jin-feng; DUAN Xiao-hong; CAO Yu-xue

    2009-01-01

    Background This retrospective study evaluated the diagnostic accuracy of 2-(F18)-fluoro-2-deoxy-D-glucose-positron emission tomography(18F-FDG-PET)/COmputed tomography(PET/CT)in the preoperative diagnosis of metastatic mediastinal and hilar lymph node in patients with non-small-cell lung cancer(NSCLC).Methods A total of 39 patients received preoperative 18F-FDG PET/CT and the postoperative biopsy.We compared preoperative PET/CT scan results with corresponding intraoperative histopathalogic findings in 39 NSCLC patients.The sensitivity,specificity,accuracy,positive and negative predictive value of 18F-FDG PET/CT were assessed.Results Histopathologic examination confirmed metastasis in 57 out of the 208 excised lymph nodes;23 of the 57 nodes were mediastinal and hilar lymph nodes.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of PET/CT in the preoperative diagnosis of mediastinal lymph node metastasis in NSCLC patients were 65%,96.8%,92%,78.5%and 90%,respectively.Conclusions PET/CT scan showed good accuracy in the preoperative diagnosis of mediastinal and hilar lymph node metastasis in the patients with NSCLC.We recommend that PET/CT scanning be used as a first-line evaluation tool for tumor diagnosis,therapy evaluation and follow-up.

  13. Estradiol stimulation enhances 18F-fluorodeoxyglucose uptake in breast cancer cells

    While 18F-FDG PET has an important role for detecting and monitoring breast carcinoma, the metabolic effects of estrogen stimulation on breast cancer cells may potentially affect their glucose handling. We therefore investigated the effect of estrogen stimulation on FDG uptake in a breast cancer cell line. Estrogen responsive human breast cancer MCF-7 cells were cultured in estrogen free media and were stimulated with 10-6∼10-11 M 17β-estradial (E2) for 2 to 72 hours. Levels of 18F-FDG uptake was measured after 40 min incubation. Cell number was assessed with MTT assays. The effect of P13-kinase inhibition was evaluated with 200 nM wortmannin added immediately before E2 stimulation. FDG uptake was significantly augmentated after 48 ∼ 72 hr stimulation by E2, with peak effects at concentrations of 10-8∼10-10M. After 48 hr stimulation with 10-9 M E2. FDG uptake averaged 176 ±6% of control levels (p<0.000). MTT assays did not show significant differences in cell number between groups at this stage. FDG uptake was also increased to 140±16% of controls after 24 hr stimulation (p<0.02), but the effect was significantly inhibited by wortmannin. Estradiol stimulation significantly enhances FDG uptake in estrogen responsive breast cancer cells, which appears to be at least partially mediated by the P13 kinase pathway. This phenomena may have important implication in interpretation of FDG uptake values for monitoring treatment response, since the patient may have different estrogen levels or may undergo antiestrogen treatment

  14. Metabolic Pattern of Asymptomatic Hip-Prosthesis by 18F-FDG-Positron-Emission-Tomography

    Joint replacement is a procedure with a major impact on the quality of life of patients with joint degenerative disease or traumatic injuries. However, some patients develop symptoms after the intervention caused by mechanical loosening or infection. Metabolic imaging by 18F-FDG-PET investigated in these patients isoften hampered by low specificity for diagnosis of possible septic vs. mechanical loosening. The reason for this shortcoming is to our opinion the unawareness of physiological remodeling processes that could be seen in asymptomatic patients. In order to overcome this drawback, we aimed to find out the physiological metabolic functional pattern in asymptomatic patients with implanted hip prosthesis Twelve patients (6 males, 6 females); mean age 73 ± 7 (range 58 - 91) years were prospectively enrolled in the study. The patients were admitted to our department for oncological referral with implanted hip prostheses. All patients explained no symptoms with regard to their implanted prosthesis. The attenuation corrected images were used for analysis. Fourteen hip prostheses in 12 patients were visually analyzed. Seven out of 14 prostheses among 12 patients showed focal periprosthetic enhanced metabolism, two of which showed two sites of enhanced uptake; whereas, the remaining five prostheses showed singular hypermetabolic areas within the periprosthetic site. The remaining seven prostheses in the other five patients showed no periprosthetic-enhanced uptake. Of the asymptomatic patients investigated, 58% showed focal enhanced periprosthetic glucose metabolism. This finding should be taken into consideration as a more probable unspecific metabolic pattern for correct interpretation of 18F-FDG-PET studies in patients with suspected septic loosening of the hip prosthesis

  15. Role of (18F) 2-fluoro-2-deoxyglucose positron emission tomography in upper gastrointestinal malignancies

    Elizabeth C Smyth; Manish A Shah

    2011-01-01

    The role of whole-body FDG [(18F) 2-fluoro-2-deoxyglucose] positron emission tomography (PET) scanning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two decades. FDG-PET has demonstrated significant efficacy in the staging, prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract, in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging tools. The sensitivity and specificity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases, but also on histological cell type, reflecting underlying disparities in glucose metabolism. The metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate significantly with both the histological tumor response to treatment and with consequent improvements in overall survival. This may offer a future paradigm of personalized treatment based on the PET response to chemotherapy. FDG-PET has been less successful in efforts to screen for and detect recurrent upper gastrointestinal malignancies, and in the detection of low volume metastatic peritoneal disease. Efforts to improve the accuracy of PET include the use of novel radiotracers such as (18F) FLT (3-deoxy-3-fluorothymidine) or 11C-choline, or fusion PET-CT with concurrent high-resolution computed tomography. This review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointestinal tract, specifically gastric, esophageal and pancreas carcinoma.

  16. Tracking of [18F]FDG-labeled natural killer cells to HER2/neu-positive tumors

    Introduction: The objective of this study was to label the human natural killer (NK) cell line NK-92 with [18F]fluoro-deoxy-glucose (FDG) for subsequent in vivo tracking to HER2/neu-positive tumors. Methods: NK-92 cells were genetically modified to NK-92-scFv(FRP5)-zeta cells, which express a chimeric antigen receptor that is specific to the tumor-associated ErbB2 (HER2/neu) antigen. NK-92 and NK-92-scFv(FRP5)-zeta cells were labeled with [18F]FDG by simple incubation at different settings. Labeling efficiency was evaluated by a gamma counter. Subsequently, [18F]FDG-labeled parental NK-92 or NK-92-scFv(FRP5)-zeta cells were intravenously injected into mice with implanted HER2/neu-positive NIH/3T3 tumors. Radioactivity in tumors was quantified by digital autoradiography and correlated with histopathology. Results: The NK-92 and NK-92-scFv(FRP5)-zeta cells could be efficiently labeled with [18F]FDG by simple incubation. Optimal labeling efficiencies (80%) were achieved using an incubation period of 60 min and additional insulin (10 IU/ml). After injection of 5x106 [18F]FDG-labeled NK-92-scFv(FRP5)-zeta cells into tumor-bearing mice, digital autoradiography showed an increased uptake of radioactivity in HER2/neu-positive tumors at 60 min postinjection. Conversely, injection of 5x106 NK-92 cells not directed against HER2/neu receptors did not result in increased uptake of radioactivity in the tumors. Histopathology confirmed an accumulation of the NK-92-scFv(FRP5)-zeta cells, but not the parental NK cells, in tumor tissues. Conclusion: The human NK cell line NK-92 can be directed against HER2/neu antigens by genetic modification. The genetically modified NK cells can be efficiently labeled with [18F]FDG, and the accumulation of these labeled NK cells in HER2/neu-positive tumors can be monitored with autoradiography

  17. An Unusual Case of Plasmablastic Lymphoma Presenting as Paravertebral Mass Evaluated by {sup 18}F-FDG PET/CT

    Treglia, Giorgio; Paone, Gaetano; Stathis, Anastasios; Ceriani, Luca; Giovanella, Luca [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

    2014-03-15

    A 60-year-old man underwent radiological investigations due to the onset of back pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed the presence of a paravertebral mass located ahead the body of the third thoracic vertebra. Based on these findings the patient underwent biopsy of the paravertebral mass, which showed the presence of a plasmablastic lymphoma. Therefore, the patient underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) for staging. Before {sup 18}F-FDG injection, the patient had fasted for at least 6 h; at the time of the radiopharmaceutical injection he presented glucose blood levels corresponding to 98 mg/dl. Images were acquired 1 h after intravenous injection of 280 MBq of {sup 18}F-FDG according to the body mass index. PET images were interpreted visually and semiquantitatively by using the maximal standardized uptake value (SUVmax). {sup 18}F-FDG PET/CT showed moderate radiopharmaceutical uptake corresponding to the paravertebral lesion (SUVmax 3.3) and diffuse uptake in the skeleton suspicious for bone marrow neoplastic involvement, with more evident hypermetabolic areas in the left scapula (SUVmax 3.7), right sixth rib (SUVmax 3.5), and left iliac bone (SUVmax 3.4) (Fig. 1). Subsequent bone marrow biopsy confirmed the bone marrow infiltration by plasmablastic cells. Based on these findings, a final diagnosis of plasmablastic lymphoma with bone marrow involvement was performed and the patient was addressed to chemotherapy. Plasmablastic lymphoma is a rare CD20-negative large-cell lymphoma with plasmablastic features occurring primarily in HIV or Epstein-Barr virus positive individuals. Distinguishing this tumor from myeloma could be challenging. The most frequent site of presentation is the oral cavity, whereas extraoral localizations of plasmablastic lymphoma are considered to be very rare and they should be differentiated from extraosseous localization of

  18. Non-malignant 18F-FDG uptake in the thorax by positron emission tomography computed tomography fusion imaging

    Fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) has been used exclusively to diagnose malignancies. However, increased FDG uptake is not always limited to malignant tissue. Many false positive findings for PET have been reported. Moreover, the use of PET/CT may allow the reassessment of previously recognized patterns of physiological bio-distribution of a tracer. In this report we demonstrate the physiological FDG uptake of normal structures in the thorax using PET/CT imaging and illustrate many benign pathological conditions with standardized uptake values greater than 2.5

  19. Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) in pancreatic cancer cell lines

    Here we report the expression of major pyrimidine metabolising enzymes in pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic cancer and the in vitro uptake of 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT). The expression of pyrimidine metabolising enzymes was evaluated with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1) activity was measured with a fluorocytometric assay. The cellular uptake and intracellular metabolism of [18F]FLT were evaluated in pancreatic lobules and in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were increased in six pancreatic cancer cell lines, while mRNA levels of thymidine kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human pancreatic cancer as compared with normal pancreatic tissue and samples from patients with chronic pancreatitis. The cellular uptake of [18F]FLT was 18.4%±3.6% and 5.2%±1.4% of the applied radioactivity after 240 min in SW-979 and BxPc-3 cells, respectively, while uptake of [18F]fluorodeoxyglucose ([18F]FDG) was only 0.6%±0.04% (SW-979) and 0.3%±0.13% (BxPc-3) after 240 min of incubation. In contrast, cellular uptake of [18F]FLT in isolated pancreatic lobules and growth-arrested HT1080 cells was lower as compared with the uptake of [18F]FDG and with the malignant pancreatic cancer cell lines. HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the phosphorylation of [18F]FLT to the respective monophosphate in both cell lines. Furthermore, 0.8%±0.12% (BxPc-3) and 1.3%±0.38% (SW-979) of the applied radioactivity was detected in the perchloric acid-insoluble cell fraction, indicating the incorporation of [18F]FLT into the DNA. Our results demonstrate the cellular uptake, intracellular trapping and incorporation into the DNA of [18F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme of [18F

  20. Performance of 18F-FDG PET/CT as a postoperative surveillance imaging modality for asymptomatic advanced gastric cancer patients

    The purpose of this study was to investigate the diagnostic performance of postoperative fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as a surveillance modality for advanced gastric cancer patients who were asymptomatic and negative by conventional follow-up. We retrospectively collected 46 advanced gastric cancer patients who received approximately 1-year-postoperative 18F-FDG PET/CT surveillance following curative resection (mean age 60.6 ± 11.5 years). 18F-FDG PET/CT was interpreted by nuclear medicine physicians who were blind to the clinical information. Final confirmation was determined by clinical follow-up using tumor markers, conventional CT scan, upper gastrointestinal endoscopy and with/without subsequent histopathologic diagnosis. Four patients developed recurrence (8.7%; 1 local and 3 distant recurrences). For local recurrence, 18F-FDG PET/CT found four hypermetabolic lesions and one was local recurrence. For distant recurrence, seven hypermetabolic lesions were found in six patients and true-positive was three lesions. False-positive cases were mainly turned out to be physiologic small bowel uptake. Regardless of the recurrence site, the sensitivity, specificity, positive predictive value and negative predictive value of 18F-FDG PET/CT were 100% (4/4, 95% confidence interval (CI) 39.6-100%), 88.1% (37/42, 95% CI 73.6-95.5%), 44.4% (4/9, 95% CI 15.3-77.3%) and 100% (37/37, 95% CI 88.3-100%), respectively in the patient-based analysis. Our study showed good specificity of postoperative surveillance 18F-FDG PET/CT for detecting recurrence. Careful caution should be made for interpreting some false-positive hypermetabolic lesions in postoperative 18F-FDG PET/CT, especially at the local anastomosis site. (author)

  1. The association of 18F-FDG PET/CT parameters with survival in malignant pleural mesothelioma

    Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). In order to determine the relationships between metabolic activity and prognosis we reviewed all 18F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes. Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUVmax was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes. 18F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials. (orig.)

  2. The diagnostic value of [18F]-FDG-PET/CT in hematopoietic radiation toxicity. A Tibet minipig model

    This study was undertaken to assess the diagnostic value of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomography ([18F]-FDG-PET/CT) in the detection of radiation toxicity in normal bone marrow using Tibet minipigs as a model. Eighteen Tibet minipigs were caged in aseptic rooms and randomly divided into six groups. Five groups (n=3/group) were irradiated with single doses of 2, 5, 8, 11 and 14 Gy of total body irradiation (TBI) using an 8-MV X-ray linear accelerator. These pigs were evaluated with [18F]-FDG-PET/CT, and their marrow nucleated cells were counted. The data were initially collected at 6, 24 and 72 h after treatment and were then collected on Days 5-60 post-TBI at 5-day intervals. At 24 and 72 h post-TBI, marrow standardized uptake value (SUV) data showed a dose-dependent decrease in the radiation dose range from 2-8 Gy. Upon long-term observation, SUV and marrow nucleated cell number in the 11-Gy and 14-Gy groups showed a continuous and marked reduction throughout the entire time course, while Kaplan-Meier curves of survival showed low survival. In contrast, the SUVs in the 2-, 5- and 8-Gy groups showed early transient increases followed by a decline from approximately 72 h through Days 5-15 and then normalized or maintained low levels through the endpoint; marrow nucleated cell number and survival curves showed approximately the same trend and higher survival, respectively. Our findings suggest that [18F]-FDG-PET/CT may be helpful in quickly assessing the absorbed doses and predicting the prognosis in patients. (author)

  3. Biodistribution and catabolism of {sup 18}F-labeled N-{epsilon}-fructoselysine as a model of Amadori products

    Hultsch, Christina [Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden (Germany)]. E-mail: ch.hultsch@fz-rossendorf.de; Hellwig, Michael [Institute of Food Chemistry, Technische Universitaet Dresden, D-01062 Dresden (Germany); Pawelke, Beate [Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden (Germany); Bergmann, Ralf [Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden (Germany); Rode, Katrin [Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden (Germany); Pietzsch, Jens [Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden (Germany); Krause, Rene [Institute of Food Chemistry, Technische Universitaet Dresden, D-01062 Dresden (Germany); Henle, Thomas [Institute of Food Chemistry, Technische Universitaet Dresden, D-01062 Dresden (Germany)

    2006-10-15

    Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-{epsilon}-fructoselysine is formed via this reaction between the {epsilon}-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[{sup 18}F]fluorobenzoate was used to modify N-{epsilon}-fructoselysine at the {alpha}-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[{sup 18}F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[{sup 18}F]fluorobenzoylated N-{epsilon}-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[{sup 18}F]fluorobenzoylated N-{epsilon}-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-{epsilon}-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.

  4. Biodistribution and catabolism of 18F-labeled N-ε-fructoselysine as a model of Amadori products

    Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-ε-fructoselysine is formed via this reaction between the ε-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-ε-fructoselysine at the α-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-ε-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-ε-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-ε-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition

  5. A standardized [18F]-FDG-PET template for spatial normalization in statistical parametric mapping of dementia.

    Della Rosa, Pasquale Anthony; Cerami, Chiara; Gallivanone, Francesca; Prestia, Annapaola; Caroli, Anna; Castiglioni, Isabella; Gilardi, Maria Carla; Frisoni, Giovanni; Friston, Karl; Ashburner, John; Perani, Daniela

    2014-10-01

    [18F]-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) is a widely used diagnostic tool that can detect and quantify pathophysiology, as assessed through changes in cerebral glucose metabolism. [18F]-FDG PET scans can be analyzed using voxel-based statistical methods such as Statistical Parametric Mapping (SPM) that provide statistical maps of brain abnormalities in single patients. In order to perform SPM, a "spatial normalization" of an individual's PET scan is required to match a reference PET template. The PET template currently used for SPM normalization is based on [15O]-H2O images and does not resemble either the specific metabolic features of [18F]-FDG brain scans or the specific morphological characteristics of individual brains affected by neurodegeneration. Thus, our aim was to create a new [18F]-FDG PET aging and dementia-specific template for spatial normalization, based on images derived from both age-matched controls and patients. We hypothesized that this template would increase spatial normalization accuracy and thereby preserve crucial information for research and diagnostic purposes. We investigated the statistical sensitivity and registration accuracy of normalization procedures based on the standard and new template-at the single-subject and group level-independently for subjects with Mild Cognitive Impairment (MCI), probable Alzheimer's Disease (AD), Frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). We found a significant statistical effect of the population-specific FDG template-based normalisation in key anatomical regions for each dementia subtype, suggesting that spatial normalization with the new template provides more accurate estimates of metabolic abnormalities for single-subject and group analysis, and therefore, a more effective diagnostic measure. PMID:24952892

  6. The association of {sup 18}F-FDG PET/CT parameters with survival in malignant pleural mesothelioma

    Klabatsa, Astero; Lang-Lazdunski, Loic [Guys and St Thomas' NHS Foundation Trust, Department of Thoracic Oncology, London (United Kingdom); Chicklore, Sugama; Barrington, Sally F.; Goh, Vicky [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Cook, Gary J.R. [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Kings College London, Clinical PET Centre, Division of Imaging Sciences and Biomedical Engineering, St Thomas' Hospital, London (United Kingdom)

    2014-02-15

    Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[{sup 18}F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT). In order to determine the relationships between metabolic activity and prognosis we reviewed all {sup 18}F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes. Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUV{sub max} was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes. {sup 18}F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials. (orig.)

  7. Novel electrophilic synthesis of 6-[{sup 18}F]fluorodopamine and comprehensive biological evaluation

    Eskola, Olli; Forsback, Sarita [Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku (Finland); Groenroos, Tove J.; Marjamaeki, Paeivi; Haaparanta, Merja [University of Turku, Medicity/PET Preclinical Imaging, Turku PET Centre, Turku (Finland); Naum, Alexandru [Haukeland University Hospital, Nuclear Medicine/PET Center, Department of Radiology, Bergen (Norway); Bergman, Joergen; Solin, Olof [Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku (Finland); Aabo Akademi University, Turku PET Centre, Accelerator Laboratory, Turku (Finland); Laenkimaeki, Sami [Kuopio University Hospital, Centre for Prehospital Emergency Care, Kuopio (Finland); Kiss, Jan [University Medical Center Freiburg, Department of Cardiovascular Surgery, Freiburg (Germany); Savunen, Timo [Turku University Hospital, Department of Surgery, Turku (Finland); Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland)

    2012-05-15

    6-[{sup 18}F]Fluorodopamine (4-(2-aminoethyl)-5-[{sup 18}F]fluorobenzene-1,2-diol, 6-[{sup 18}F]FDA) is a tracer for imaging sympathetically innervated tissues. Previous electrophilic labelling methods produced 6-[{sup 18}F]FDA with low specific radioactivity (SA) which has limited its wider use. Our aim was to employ electrophilic labelling and increase the SA to around 15 GBq/{mu}mol. We also sought to determine an extensive biodistribution pattern for 6-[{sup 18}F]FDA in rats in order to thoroughly identify tissues with dense sympathetic innervation that were specifically labelled with 6-[{sup 18}F]FDA. In addition, to investigate the safety profile of 6-[{sup 18}F]FDA in larger animals, we performed in vivo studies in pigs. 6-[{sup 18}F]FDA was synthesised using high SA electrophilic [{sup 18}F]F{sub 2} as the labelling reagent. Biodistribution and metabolism of 6-[{sup 18}F]FDA was determined ex vivo in rats, and in vivo studies were done in pigs. 6-[{sup 18}F]FDA was synthesised with 2.6 {+-} 1.1% radiochemical yield. The total amount of purified 6-[{sup 18}F]FDA was 663 {+-} 291 MBq at the end of synthesis (EOS). SA, decay corrected to EOS, was 13.2 {+-} 2.7 GBq/{mu}mol. Radiochemical purity exceeded 99.0%. Specific uptake of 6-[{sup 18}F]FDA was demonstrated in heart, lung, pancreas, adrenal gland, lower large intestine (LLI), eye, thyroid gland, spleen and stomach tissue. 6-[{sup 18}F]FDA in rat plasma declined rapidly, with a half-life of 2 min, indicating fast metabolism. In vivo PET studies in pigs confirmed the tracer could be used safely without pharmacological effects. 6-[{sup 18}F]FDA was synthesised with good radiopharmaceutical quality and yields high enough for several human PET studies. The SA of 6-[{sup 18}F]FDA was improved by 50- to 500-fold compared to previous electrophilic methods. Uptake of 6-[{sup 18}F]FDA was specific in various peripheral organs, indicating that 6-[{sup 18}F]FDA PET can be used to investigate sympathoneural functions

  8. 18F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by 18F-FDOPA PET-CT

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. 18F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (18F-FDOPA) PET-CT was done, 5 days after 18F-FDG PET-CT. The study revealed an 18F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. 18F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. 18F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its

  9. {sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT

    Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

    2013-12-15

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake

  10. Niobium sputtered Havar foils for the high-power production of reactive [18F]fluoride by proton irradiation of [18O]H2O targets.

    Wilson, J S; Avila-Rodriguez, M A; Johnson, R R; Zyuzin, A; McQuarrie, S A

    2008-05-01

    Niobium sputtered Havar entrance foils were used for the production of reactive [(18)F]fluoride by proton irradiation of [(18)O]H(2)O targets under pressurized conditions. The synthesis yield in the routine production of 2-[(18)F]fluoro-2-deoxy-glucose (FDG) was used as an indicative parameter of the reactivity of (18)F. The yield of FDG obtained with (18)F produced in a target with Havar foil was used as a baseline. No statistically significant difference was found in the saturated yields of (18)F when using Havar or Havar-Nb sputtered entrance foils. However, the amount of long-lived radionuclidic impurities decreased more than 10-fold using the Havar-Nb entrance foil. The average decay corrected synthesis yield of FDG, evaluated over a period of more than 2 years, was found to be approximately 5% higher when using a Havar-Nb entrance foil and a marked improvement on the FDG yield consistency was noted. In addition, the frequency of target rebuilding was greatly diminished when using the Nb sputtered entrance foil. PMID:18242099

  11. Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and 18F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

    Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells 18F fluorodeoxyglucose (18F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased 18F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of 18F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with 18F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case

  12. Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and {sup 18}F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

    KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh [India Institute of Medical Sciences, New Delhi (India)

    2012-12-15

    Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells {sup 18}F fluorodeoxyglucose ({sup 18}F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased {sup 18}F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of {sup 18}F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with {sup 18}F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case.

  13. Single dose toxicity and biodistribution studies of [18F] fluorocholine

    [18F]Fluorocholine (18FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  14. Evaluation of steam sterilization conditions for [18F]fludeoxyglucose

    [18F]Flu deoxyglucose (18FDG) 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 18FDG. 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 18FDG. 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. 18FDG pH-formulation was kept around 6.0. At the end of autoclave cycles, 18FDG sterility was evaluated by direct inoculation of 18FDG in culture media and radiochemical purity was determined by TLC and HPLC. Results demonstrated that all essayed conditions were able to ensure 18FDG sterility, but caused a decrease in radiochemical purity of 18FDG. Autoclave cycle at 133 deg C for 2 minutes was the best essayed condition for 18FDG terminal sterilization, once it provided the greater radiochemical purity value and took less time. 18FDG was able to meet specifications after autoclave cycles, what supports the application of steam sterilization in routine 18FDG production, in compliance with GMP. (author)

  15. Imaging multidrug resistance with 4-[{sup 18}F]fluoropaclitaxel

    Kurdziel, Karen A. [Department of Radiology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: kurdziel@vcu.edu; Kalen, Joseph D. [School of Medicine, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: jdkalen@vcu.edu; Hirsch, Jerry I. [School of Medicine, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: jihirsch@vcu.edu; Wilson, John D. [School of Medicine, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: wilsonjd@hsc.vcu.edu; Agarwal, Rakesh [Surgical Oncology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: dbarrett@vcu.edu; Barrett, Daniel [School of Medicine, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: ragarwal@vcu.edu; Bear, Harry D. [Surgical Oncology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: 9jmccumi@mail2.vcu.edu; McCumiskey, James F. [Department of Radiology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: hbear@hsc.vcu.edu

    2007-10-15

    Multidrug resistance (MDR) is a cause of treatment failure in many cancer patients. MDR refers to a phenotype whereby a tumor is resistant to a large number of natural chemotherapeutic drugs. Having prior knowledge of the presence of such resistance would decrease morbidity from unsuccessful therapy and allow for the selection of individuals who may benefit from the coadministration of MDR-inhibiting drugs. The Tc-99m-labeled single-photon-emitting radiotracers sestamibi and tetrofosmin have shown some predictive value. However, positron-emitting radiotracers, which allow for dynamic quantitative imaging, hold promise for a more accurate and specific identification of MDRtumors.MDR-expressing tumors are resistant to paclitaxel, which is commonly used as a chemotherapeutic agent. 4-[{sup 18}F]Fluoropaclitaxel (FPAC) is a PET-radiolabeled analogue of paclitaxel. Preclinical studies have shown the uptake of FPAC to be inversely proportional to tumor MDR expression. FPAC PET imaging in normal volunteers shows biodistribution to be similar to that in nonhuman primates. Imaging in a breast cancer patient showed FPAC localization in a primary tumor that responded to chemotherapy, while failure to localize in mediastinal disease corresponded with only partial response.FPAC PET imaging shows promise for the noninvasive pretreatment identification of MDR-expressing tumors. While much additional work is needed, this work represents a step toward image-guided personalized medicine.

  16. A novel radiochemical approach to 1-(2'-deoxy-2'-[(18) F]fluoro-β-d-arabinofuranosyl)cytosine ((18) F-FAC).

    Meyer, Jan-Philip; Probst, Katrin C; Trist, Iuni M L; McGuigan, Christopher; Westwell, Andrew D

    2014-09-01

    (18) F-FAC (1-(2'-deoxy-2'-[(18) F]fluoro-β-D-arabinofuranosyl)-cytosine) is an important 2'-fluoro-nucleoside-based positron emission tomography (PET) tracer that has been used for in vivo prediction of response to the widely used cancer chemotherapy drug gemcitabine. Previously reported synthetic routes to (18) F-FAC have relied on early introduction of the (18) F radiolabel prior to attachment to protected cytosine base. Considering the (18) F radiochemical half-life (110 min) and the technical challenges of multi-step syntheses on PET radiochemistry modular systems, late-stage radiofluorination is preferred for reproducible and reliable radiosynthesis with in vivo applications. Herein, we report the first late-stage radiosynthesis of (18) F-FAC. Cytidine derivatives with leaving groups at the 2'-position are particularly prone to undergo anhydro side-product formation upon heating because of their electron density at the 2-carbonyl pyrimidone oxygen. Our rationally developed fluorination precursor showed an improved reactivity-to-stability ratio at elevated temperatures. (18) F-FAC was obtained in radiochemical yields of 4.3-5.5% (n = 8, decay-corrected from end of bombardment), with purities ≥98% and specific activities ≥63 GBq/µmol. The synthesis time was 168 min. PMID:25257474

  17. An efficient synthesis of dopamine transporter tracer [18F]FECNT

    A simple synthesis of the dopamine transporter ligand [18F]FECNT with high radiochemical yield and short synthesis time, suitable for routine production is reported. Reaction of 2β-carbomethoxy-3β-(4-chlorophenyl)nortropane with [18F]2-fluoroethyl triflate ([18F]FEtOTf) at room temperature for 4 min provided [18F]FECNT in 84% decay corrected radiochemical yield. Since [18F]FEtOTf was prepared from [18F]2-fluoroethyl bromide that was isolated from its starting material, formation of unwanted side products and the amount of expensive precursor used could be greatly reduced. The overall radiochemical yields of [18F]FECNT were 40% (n=29) and the total synthesis time was ca. 100 min. The average specific activity of [18F]FECNT was 377.4 GBq/μmol (10.2 Ci/μmol). - Highlights: ► An efficient synthesis of dopamine transporter tracer [18F]FECNT is presented. ► Coupling using isolated labeling synthon reduces side products formation. ► Higher radiochemical yields and mild reaction conditons achieved. ► Very low amounts of expensive precursor used reducing the cost per synthesis. ► Suitable for routine production of [18F]FECNT.

  18. 18F-fluoride PET imaging in a nude rat model of bone metastasis from breast cancer: Comparison with 18F-FDG and bioluminescence imaging

    Introduction: Clinically-relevant animal models and appropriate imaging diagnostic tools are essential to study cancer and develop novel therapeutics. We evaluated a model of bone metastasis in nude rats by micro-PET and bioluminescence imaging. Methods: A bone metastasis model was produced by intracardiac injection of osteotropic MDA-MB-231Bo-Luc human breast cancer cells into nude rats. Bioluminescence imaging and micro-PET scans using 18F-FDG and 18F-fluoride were acquired serially for 5 weeks. We correlated bioluminescence imaging, 18F-FDG and 18F-fluoride PET images, and histological slides. Results: Multiple bone metastases were successfully evaluated by bioluminescence imaging and 18F-FDG and 18F-fluoride PET scans. Bioluminescence photon flux increased exponentially on weekly follow-up. 18F-FDG PET revealed increased FDG uptake at the spine and bilaterally in the hind legs in week 2 images, and showed a progressive pattern up to 4 weeks that correlated with bioluminescence imaging. 18F-fluoride PET showed minimal abnormal findings in week 2 images, but it showed an irregular pattern at the spine from week 3 or 4 images. On quantitative analysis with standardized uptake values, a pattern of gradual increase was observed from week 2 to week 4 in both 18F-FDG PET and fluoride PET. Histopathological examination confirmed the formation of osteolytic metastasis and necrosis of the distal femur, which appeared as a photon defect on PET scans. Conclusion: Developing bone metastasis from breast cancer in a nude rat model was successfully evaluated with an animal PET imaging system and bioluminescence imaging. This nude rat model of bone metastasis, which can be evaluated by PET imaging, may be a valuable tool for evaluating early responses to novel therapeutics

  19. {sup 18}F-FLT and {sup 18}F-FDOPA PET kinetics in recurrent brain tumors

    Wardak, Mirwais; Schiepers, Christiaan; Dahlbom, Magnus; Phelps, Michael E.; Huang, Sung-Cheng [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Cloughesy, Timothy F. [David Geffen School of Medicine at UCLA, Department of Neurology, Los Angeles, CA (United States)

    2014-06-15

    In this study, kinetic parameters of the cellular proliferation tracer {sup 18}F-3'-deoxy-3'-fluoro-l-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-{sup 18}F-fluoro-l-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis. High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models. Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R{sup 2} = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R{sup 2} = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R{sup 2} = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R{sup 2} = 0.25). For recurrent malignant glioma treated

  20. Preliminary evaluation of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts

    Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [18F]FDG, has inadequate resolution for detection of small (2–3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an 18F-labelled lactose derivative, [18F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[18F]fluoroethyl lactose ([18F]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice. Methods: Xenografts were developed in nude mice by injecting L3.6pl/GL+ pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2–3 mm, the animals were injected with [18F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [18F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results: Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [18F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [18F]FEL in the peritumoural pancreatic tissue was 1.29 ± 0.295 %ID/g, and that in the normal pancreas of control animals was 0.090 ± 0.101 %ID/g. [18F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [18F]FEL binding and HIP

  1. 18F-FDG PET analysis of schwannoma: increase of SUVmax in the delayed scan is correlated with elevated VEGF/VPF expression in the tumors

    In order to clarify the increased 2-deoxy-2-fluoro-18F-d-glucopyranose (18F-FDG) accumulation in schwannoma by positron emission tomography (PET) analysis, immunohistochemical analysis for the factors involved in glucose transportation and vascular formation was performed. Twenty-six patients with schwannoma (13 men and 13 women) with ages ranging from 27 to 75 years, who received whole body 18F-FDG PET scan, were enrolled for the present study. The retention index (RI) was calculated by dividing the increase in the standardized uptake value (SUVmax) at the delayed scan by the SUVmax in the early scan. SUVmax and RI were compared with the histologic variables, including the expression of glucose transporters 1 and 3, hexokinase II, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), and microvascular density shown by CD31 immunohistochemistry. Mean SUVmax values in the early and delayed scans were 2.64±1.47 and 2.71±1.57 (mean ± SD), respectively. RI was -2.5±21 (percentage). SUVmax showed a positive correlation with the tumor size (tumor size 5 cm, 3.95±1.89; p18F-FDG accumulation in schwannoma. (orig.)

  2. Novel Method for Radiolabeling and Dimerizing Thiolated Peptides Using (18)F-Hexafluorobenzene.

    Jacobson, Orit; Yan, Xuefeng; Ma, Ying; Niu, Gang; Kiesewetter, Dale O; Chen, Xiaoyuan

    2015-10-21

    Hexafluorobenzene (HFB) reacts with free thiols to produce a unique and selective perfluoroaromatic linkage between two sulfurs. We modified this chemical reaction to produce dimeric (18)F-RGD-tetrafluorobenzene (TFB)-RGD, an integrin αvβ3 receptor ligand. (18)F-HFB was prepared by a fluorine exchange reaction using K(18)F/K2.2.2 at room temperature. The automated radiofluorination was optimized to minimize the amount of HFB precursor and, thus, maximize the specific activity. (18)F-HFB was isolated by distillation and subsequently reacted with thiolated c(RGDfk) peptide under basic and reducing conditions. The resulting (18)F-RGD-TFB-RGD demonstrated integrin receptor specific binding, cellular uptake, and in vivo tumor accumulation.(18)F-HFB can be efficiently incorporated into thiol-containing peptides at room temperature to provide novel imaging agents. PMID:26086295

  3. Synthesis of new hypoxia markers EF1 and [18F]-EF1

    We report on the preparation of a hypoxia marker 2-(2-nitroimidazol-1[H]-yl)-N-(3-fluoropropyl)acetamide (EF1) and its 18F analog, 2-(2-nitroimidazol-1[H]-yl)-N-(3-[18F]fluoropropyl)acetamide ([18F]-EF1). Two methods for the preparation of 3-fluoropropylamine, the EF1 side chain, are described. [18F]-EF1 was prepared with a radiochemical yield of 2% by nucleophilic substitution of bromine in 2-(2-nitroimidazol-1[H]-yl)-N-(3-bromopropyl)acetamide (EBr1) by carrier-added 18F in DMSO at 120 deg. C. Our results demonstrate the preparation of clinically relevant amounts of [18F]-EF1 for use as a non-invasive hypoxia marker with detection using positron emission tomography (PET)

  4. The Semi-automatic Synthesis of 18F-fluoroethyl-choline by Domestic FDG Synthesizer

    ZHOU Ming

    2016-02-01

    Full Text Available As an important complementary imaging agent for 18F-FDG, 18F-fluoroethyl-choline (18F-FECH has been demonstrated to be promising in brain and prostate cancer imaging. By using domestic PET-FDG-TI-I CPCU synthesizer, 18F-FECH was synthesized by different reagents and consumable supplies. The C18 column was added before the product collection bottle to remove K2.2.2. The 18F-FECH was synthesized by PET-FDG-IT-I synthesizer efficiently about 30 minutes by radiochemical yield of 42.0% (no decay corrected, n=5, and the radiochemical purity was still more than 99.0% after 6 hours. The results showed the domestic PET-FDG-IT-I synthesizer could semi-automatically synthesize injectable 18F-FECH in high efficiency and radiochemical purity

  5. Improved quality control of [18F]fluoromethylcholine

    Objectives: With respect to the broad application of [18F-methyl]fluorocholine (FCH), there is a need for a safe, but also efficient and convenient way for routine quality control of FCH. Therefore, a GC- method should be developed and validated which allows the simultaneous quantitation of all chemical impurities and residual solvents such as acetonitrile, ethanol, dibromomethane and N,N-dimethylaminoethanol. Methods: Analytical GC has been performed with a GC-capillary column Optima 1701 (50 m×0.32 mm), and a pre-column deactivated capillary column phenyl-Sil (10 m×0.32) in line with a flame ionization detector (FID) was used. The validation includes the following tests: specificity, range, accuracy, linearity, precision, limit of detection (LOD) and limit of quantitation (LOQ) of all listed substances. Results: The described GC method has been successfully used for the quantitation of the listed chemical impurities. The specificity of the GC separation has been proven by demonstrating that the appearing peaks are completely separated from each other and that a resolution R≥1.5 for the separation of the peaks could be achieved. The specified range confirmed that the analytical procedure provides an acceptable degree of linearity, accuracy and precision. For each substance, a range from 2% to 120% of the specification limit could be demonstrated. The corresponding LOD values were determined and were much lower than the specification limits. Conclusions: An efficient and convenient GC method for the quality control of FCH has been developed and validated which meets all acceptance criteria in terms of linearity, specificity, precision, accuracy, LOD and LOQ.

  6. Analysis of Imaging Characteristics of18F-FDG PET/CT in Misdiagnosed Bone Tuberculosis:A Report of 12 Cases

    DING Qi-yong; LI Tian-nyu; CHEN Jian-wei; LIU Lian-ke

    2015-01-01

    Objective: To analyze the imaging characteristics of18F-lfuorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) in 12 cases of misdiagnosed bone tuberculosis so as to explore the differential diagnostic method with metastatic bone tumors. Methods: The images of 12 patients with bone tuberculosis diagnosed by18F-FDG PET/CT were retrospectively analyzed. Distribution of lesion locations in the whole body and characteristics of glucose metabolism were analyzed by qualitative and semi-quantitative methods, especially for bone lesion location, number and range, glucose uptake form and CT imaging characteristics, and the maximum of standardized uptake value (SUVmax) was measured and recorded. Results: Of 12 patients, 1 showed increased glucose uptake of diffuse bone marrow in the whole body, whereas the rest suffered from 19 bone lesions, in which each one had 1 bone lesion in 9 cases, accounting for 75.0%. The images of PET/CT in 12 patients primarily manifested annular or nonuniform increase of glucose uptake (63.2%), sequestrum within osteolytic lesions (31.6%), injured intervertebral disc caused by vertebral lesions (61.5%) and cold abscesses around the lesions (68.4%). The glucose uptake rate of cold abscesses was higher than that of bone lesion locations. The tuberculosis complicated with other parts included lymphatic tuberculosis (100.0%), pulmonary tuberculosis (66.7%), pericardial or pleural tuberculosis (25.0%) and hepatolienal tuberculosis (8.3%). Conclusion: The characteristics of bone tuberculosis lesions are prominent in18F-FDG PET/CT imaging, which could contribute to diagnosis of whole body tuberculosis and has a greater value in the differentiation of bone tuberculosis and metastatic bone tumors.

  7. 18F-FDG SPECT myocardial imaging of right ventricle in patients with idiopathic pulmonary hypertension

    was (21 ±8) months. Mean survival time for the patients with RV/LV- FDG uptake ≥ 1.15 was 28 months (95% confidence interval: 24-32 months), which was significantly lower than 34 months survival (95% confidence interval: 33-35 months) for the patients with RV/LV-FDG <1.15 (χ2=3.956, P>0.05). Conclusions: Detection of right ventricle myocardial glucose metabolism level with 18F-FDG SPECT may be a practical method for evaluating haemodynamic change, treatment outcome and prognosis of IPAH. (authors)

  8. Reproducibility of Intratumor Distribution of 18F-Fluoromisonidazole in Head and Neck Cancer

    Purpose: Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of 18F-FMISO intratumor distribution using two pretreatment PET scans. Methods and Materials: We enrolled 20 head and neck cancer patients in this study. Of these, 6 were excluded from the analysis for technical reasons. All patients underwent an 18F-fluorodeoxyglucose study, followed by two 18F-FMISO studies 3 days apart. The hypoxic volumes were delineated according to a tumor/blood ratio ≥1.2. The 18F-FMISO tracer distributions from the two 18F-FMISO studies were co-registered on a voxel-by-voxel basis using the computed tomography images from the PET/computed tomography examinations. A correlation between the 18F-FMISO intensities of the corresponding spatial voxels was derived. Results: A voxel-by-voxel analysis of the 18F-FMISO distributions in the entire tumor volume showed a strong correlation in 71% of the patients. Restraining the correlation to putatively hypoxic zones reduced the number of patients exhibiting a strong correlation to 46%. Conclusion: Variability in spatial uptake can occur between repeat 18F-FMISO PET scans in patients with head and neck cancer. Blood data for one patient was not available. Of 13 patients, 6 had well-correlated intratumor distributions of 18F-FMISO-suggestive of chronic hypoxia. More work is required to identify the underlying causes of changes in intratumor distribution before single-time-point 18F-FMISO PET images can be used as the basis of hypoxia-targeting intensity-modulated radiotherapy

  9. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    Vadim Bernard-Gauthier; Carmen Wängler; Esther Schirrmacher; Alexey Kostikov; Klaus Jurkschat; Bjoern Wängler; Ralf Schirrmacher

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in part...

  10. Clinical Application of 18F-FDG PET in Multiple Myeloma

    This review focuses on the clinical use of 18F-FDG PET to evaluate multiple myeloma. 18F-FDG PET is useful for diagnosis, staging of multiple myeloma and differential diagnosis of myeloma related disease such as monoclonal gammopathy of undetermined significance or plasmacytoma. For therapy response, 18F-FDG PET may be effective after chemotherapy for multiple myeloma and radiotherapy for plasmacytoma

  11. Clinical Application of {sup 18}F-FDG PET in Testicular Cancer

    Yoon, Joon Kee [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2008-12-15

    {sup 18}F-FDG PET has a higher diagnostic accuracy than CT in initial staging of testicular cancer. In seminoma, it can discriminate residual tumor from necrosis/fibrosis or mature teratoma. {sup 18}F-FDG PET is also useful for the response evaluation of chemotherapy. However, there's no clinical evidence for the use of {sup 18}F-FDG PET in the diagnosis and differential diagnosis of testicular cancer.

  12. Evaluation of [18F]-(-)-norchlorofluorohomoepibatidine ([18F]-(-)-NCFHEB) as a PET radioligand to image the nicotinic acetylcholine receptors in non-human primates

    Introduction: The aims of the present study were to develop an optimized microfluidic method for the production of the selective nicotinic acetylcholine α4β2 receptor radiotracer [18F]-(-)-NCFHEB ([18F]-Flubatine) and to investigate its receptor binding profile and pharmacokinetic properties in rhesus monkeys in vivo. Methods: [18F]-(-)-NCFHEB was prepared in two steps, a nucleophilic fluorination followed by N-Boc deprotection. PET measurements were performed in rhesus monkeys including baseline and preblocking experiments with nicotine (0.24 mg/kg). Radiometabolites in plasma were measured using HPLC. Results: [18F]-(-)-NCFHEB was prepared in a total synthesis time of 140 min. The radiochemical purity in its final formulation was > 98% and the mean specific radioactivity was 97.3 ± 16.1 GBq/μmol (n = 6) at end of synthesis (EOS). In the monkey brain, radioactivity concentration was high in the thalamus, moderate in the putamen, hippocampus, frontal cortex, and lower in the cerebellum. Nicotine blocked 98-100% of [18F]-(-)-NCFHEB specific binding, and the non-displaceable distribution volume (VND) was estimated at 5.9 ± 1.0 mL/cm3 (n = 2), or 6.6 ± 1.1 mL/cm3 after normalization by the plasma free fraction fP. Imaging data are amenable to kinetic modeling analysis using the multilinear analysis (MA1) method, and model-derived binding parameters display good test-retest reproducibility. In rhesus monkeys, [18F]-(-)-NCFHEB can yield robust regional binding potential (BPND) values (thalamus = 4.1 ± 1.5, frontal cortex = 1.2 ± 0.2, putamen = 0.96 ± 0.45, and cerebellum = 0.10 ± 0.29). Conclusion: An efficient microfluidic synthetic method was developed for preparation of [18F]-(-)-NCFHEB. PET examination in rhesus monkeys showed that [18F]-(-)-NCFHEB entered the brain readily and its regional radioactivity uptake pattern was in accordance with the known distribution of α4β2 receptors. Estimated non-displaceable binding potential (BPND) values in brain

  13. [{sup 18}F]FDG PET monitoring of tumour response to chemotherapy: does [{sup 18}F]FDG uptake correlate with the viable tumour cell fraction?

    Spaepen, Karoline; Stroobants, Sigrid; Dupont, Patrick; Bormans, Guy; Mortelmans, Luc [Department of Nuclear Medicine, UZ Gasthuisberg, Herestraat 49, 3000, Leuven (Belgium); Balzarini, Jan [Rega Institute, Katholieke Universiteit, Leuven (Belgium); Verhoef, Gregor; Vandenberghe, Peter [Department of Hematology, UZ Gasthuisberg, Leuven (Belgium); De Wolf-Peeters, Christine [Department of Pathology, UZ Gasthuisberg, Leuven (Belgium)

    2003-05-01

    Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [{sup 18}F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [{sup 18}F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10{sup 6} Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [{sup 18}F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [{sup 18}F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [{sup 18}F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [{sup 18}F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [{sup 18}F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells. (orig.)

  14. 18F-fluoromisonidazole (FMISO) and 18F-fluorodeoxyglucose (FDG) PET in patients undergoing radiotherapy or chemotherapy following surgery for high-grade glioma

    Full text:Background: Tumour hypoxia is associated with disease progression and resistance to therapy. High grade cerebral gliomas have a poor outcome despite advancements in chemotherapy and radiotherapy. 18F-fluoromisonidazole (18F-FMISO) concentrates in hypoxic cells and is associated with tumour grade in gliomas. The aim of this study was to compare the patterns of uptake of 18F-FDG PET and 18F-FMISO PET post-surgery with MRI and areas of recurrence post-radiotherapy. Methods: Patients with high grade cerebral glioma were recruited into this prospective study. All patients had post-surgical, pre-radiotherapy 18F-FDG, 18F-FMISO and MRI scans, which were all repeated 4-6 weeks post-completion to radiotherapy. The patients were followed-up clinically three monthly and re-imaged if indicated. Results: Ten patients were enrolled in this study, mean age 62 years (range 55-69 years), who all had pre-radiotherapy scans performed. Seven patients had scans done pre- and post-radiotherapy, with 3 patients with only pre-therapy scans. Nine patients had significant FMISO uptake and 8 patients demonstrated abnormal FDG uptake. The areas of FMISO uptake on pre-radiotherapy scans correlated with the most abnormal areas of contrast-enhancement on pre-treatment MRI and areas of locally recurrent disease on post-treatment MRI in eight patients. Nine patients had locally recurrent disease on follow-up MRI. FMISO was more predictive of tumour recurrence compared to FDG. Conclusion: Post-surgical 18F-FMISO PET in patients with cerebral glioma is more predictive of areas of recurrent disease compared to 18F-FDG PET.

  15. Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

    Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2010-03-15

    In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

  16. Artifacts and pitfalls in oncologic {sup 18}F-FDG-PET-CT imaging; Artefakte und Fallstricke in der onkologischen {sup 18}F-FDG-PET-CT-Diagnostik

    Falck, Christian von [Medizinische Hochschule Hannover (Germany). Schwerpunkt multimodale Bildgebung; Raatschen, Hans-Juergen [Charite Berlin (Germany). Radiologie; Bengel, Frank M. [Medizinische Hochschule Hannover (Germany)

    2011-12-15

    Hybrid imaging such as {sup 18}F-FDG PET-CT synergistically combines the advantages of metabolic and morphologic imaging. Due to its increasing role in the imaging of oncologic disease there is a growing demand for the general radiologists to have a basic unterstanding of the method and its limitations. Therefore, the objective of this review is to explain und illustrate the typical artifacts and pitfalls of oncologic PET-CT imaging using {sup 18}F-FDG. (orig.)

  17. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  18. Incidental gastrointestinal 18F-Fluorodeoxyglucose uptake associated with lung cancer

    Vella-Boucaud, Juliette; Papathanassiou, Dimitri; Bouche, Olivier; Prevost, Alain; Lestra, Thibault; Dury, Sandra; Vallerand, Hervé; Perotin, Jeanne-Marie; Launois, Claire; Boissiere, Louis; Brasseur, Mathilde; Lebargy, François; Deslee, Gaëtan

    2015-01-01

    Background F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is increasingly used for the initial staging and restaging of lung cancer. Incidental gastrointestinal findings are often observed on 18F-FDG PET/CT. The objective of this study was to assess incidental 18F-FDG uptake by the gastrointestinal tract (GIT) in patients with lung cancer. Methods Two hundred thirty consecutive 18F-FDG PET/CT examinations performed for lung cancer over a 3-year period w...

  19. Reduced dimethylaminoethanol in [18F]fluoromethylcholine: an important step towards enhanced tumour visualization

    [18F]Fluoromethylcholine ([18F]FCho) is a radiotracer generally used for tumour visualization in patients. Due to high levels of dimethylaminoethanol (DMAE) remaining in [18F]FCho solutions synthesized by currently available methods, tumour visualization might be compromised. An improved purification method involving an optimized purification step for reducing the levels of DMAE was conceived. The physiological explanation for the interference of residual DMAE in [18F]FCho pharmacokinetics was further elaborated in a xenograft mouse model. The use of a series of polymer solid-phase extraction cartridges (Oasis HLB/WCX), instead of the commonly used combination of tC18 and Accell CM cartridges, reduced DMAE levels from 402.2±49.6 ppm to 3.0±0.5 ppm. Subsequent in vitro tests proved that (1) [18F]FCho uptake was reduced in the presence of DMAE at concentrations above 0.5 μM and (2) DMAE is a competitive inhibitor of [18F]FCho transport. In vivo experiments in xenograft mouse models corroborated reduced tumour uptake at DMAE plasma levels of about 2.5 μM as found in patients injected with contaminated [18F]FCho. Residual DMAE, even at levels below choline plasma concentrations found during fasting, compromises [18F]FCho uptake in vivo and care should be taken to avoid its interference in molecular imaging with [18F]FCho. (orig.)

  20. Reduced dimethylaminoethanol in [{sup 18}F]fluoromethylcholine: an important step towards enhanced tumour visualization

    Slaets, Dominique; Bruyne, Sylvie de; Dumolyn, Caroline; Moerman, Lieselotte; Vos, Filip de [Ghent University, Laboratory of Radiopharmacy, Faculty Pharmaceutical Sciences (Belgium); Mertens, Koen [Ghent University, Department of Nuclear Medicine (Belgium)

    2010-11-15

    [{sup 18}F]Fluoromethylcholine ([{sup 18}F]FCho) is a radiotracer generally used for tumour visualization in patients. Due to high levels of dimethylaminoethanol (DMAE) remaining in [{sup 18}F]FCho solutions synthesized by currently available methods, tumour visualization might be compromised. An improved purification method involving an optimized purification step for reducing the levels of DMAE was conceived. The physiological explanation for the interference of residual DMAE in [{sup 18}F]FCho pharmacokinetics was further elaborated in a xenograft mouse model. The use of a series of polymer solid-phase extraction cartridges (Oasis HLB/WCX), instead of the commonly used combination of tC18 and Accell CM cartridges, reduced DMAE levels from 402.2{+-}49.6 ppm to 3.0{+-}0.5 ppm. Subsequent in vitro tests proved that (1) [{sup 18}F]FCho uptake was reduced in the presence of DMAE at concentrations above 0.5 {mu}M and (2) DMAE is a competitive inhibitor of [{sup 18}F]FCho transport. In vivo experiments in xenograft mouse models corroborated reduced tumour uptake at DMAE plasma levels of about 2.5 {mu}M as found in patients injected with contaminated [{sup 18}F]FCho. Residual DMAE, even at levels below choline plasma concentrations found during fasting, compromises [{sup 18}F]FCho uptake in vivo and care should be taken to avoid its interference in molecular imaging with [{sup 18}F]FCho. (orig.)

  1. Clinical impact of 18F-FDG PET/CT on suspected cervical cancer recurrence

    Objective: To evaluate the clinical impact of 18F-FDG PET/CT on patients with suspected cervical cancer recurrence. Methods: Fifty-one cervical cancer patients, clinically suspected to have tumor recurrence during follow-up, underwent 18F-FDG PET/CT examination. 18F-FDG PET/CT results were compared with those of conventional images, as referred to histopathology or clinical follow-up. Impacts of 18F-FDG PET/CT were evaluated based on documented changes of clinical management. Results: In total, 43 patients were found to have positive lesions by 18F-FDG PET/CT, in which 40 were true recurrence,but 2 were pelvic abscess and 1 was radiation enterocolitis. Other 8 patients were found negative by 18F-FDG PET/CT and confirmed by pathology or follow-up. In patient-based analyses, the sensitivity, specificity, and accuracy of 18F-FDG PET/CT for the detection of tumor recurrence were 100% (40/40), 72.73% (8/11), and 94.12% (48/51) respectively. In 7 patients, the clinical management was changed due to 18F-FDG PET/CT findings. Conclusion: 18F-FDG PET/CT is an efficient tool for determining the recurrence of cervical cancer and instructing the clinical management. (authors)

  2. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  3. Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study

    We analyzed 18F-dopa PET data from 11 members of kindreds with familial progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic dysfunction. Three clinically-affected PSP patients showed reduced 18F-dopa uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic subject exhibited progressive putamen dopaminergic dysfunction. 60 % of subjects with abnormal 18F-dopa scans developed PSP subsequently. This is the first in vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal 18F-dopa uptake in susceptible relatives may predict later clinical disease. (author)

  4. Synthesis of [18F]fluoroetanidazole: A potential new tracer for imaging hypoxia

    A method has been developed for the synthesis of [18F]fluoroetanidazole, a potential tracer for imaging hypoxia with positron emission tomography. The compound is prepared by an active ester coupling reaction between the 2,3,5,6-tetrafluorophenyl ester of 2-nitroimidazole acetic acid and [18F]fluoroethylamine. [18F]Fluoroethylamine is prepared from N-[2-(toluene-4-sulfonyloxy)-ethyl]-phthalimide and [18F]fluoride and purified by distillation. The overall reaction takes about 90 min and gives a yield, uncorrected, of about 25%. Purification on a reversed-phase column is straightforward

  5. Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus

    Although positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is a promising imaging modality for bone infections, the technique may still give false-positive results due to unspecific uptake in healing bone. This experimental study compared 18F-FDG and 68Ga in PET imaging of osteomyelitis and normal bone healing. A diffuse osteomyelitis model of the tibia was applied in the rat (n=50). Two weeks after operation, PET imaging with 18F-FDG and 68Ga was performed, followed by peripheral quantitative computed tomography (pQCT) and radiography. Osteomyelitis was verified by quantitative bacteriology. In addition to in vivo imaging, ex vivo measurements of tissue radioactivity were performed to verify uptake of the tracers. Compared with controls with normal bone healing, the osteomyelitic tibias showed increased SUV ratios (i.e. radioactivity ratios between the operated and non-operated sides) for both 18F-FDG (1.74±0.37) and 68Ga (1.62±0.28) (P18F-FDG and P68Ga). The intensity of 68Ga uptake reflected pathological changes of osteomyelitic bones measured by pQCT. The uptake of 18F-FDG, however, did not show as close a correlation with the anatomical changes. The healing bones without infection exhibited slightly elevated uptake of 18F-FDG (SUV ratio 1.16±0.06), but 68Ga did not accumulate in the healing bone, as judged on the basis of both in vivo imaging (SUV ratio 1.02±0.05) and ex vivo measurements (SUV 0.92±0.21) (P=0.003 and P=0.022 compared with 18F-FDG uptake, respectively). This study suggests the feasibility of 68Ga PET imaging of bone infections. However, further studies are needed to clarify the value of 68Ga PET for clinical purposes. (orig.)

  6. Improved synthesis of [18F]FLETT via a fully automated vacuum distillation method for [18F]2-fluoroethyl azide purification

    The synthesis of [18F]2-fluoroethyl azide and its subsequent click reaction with 5-ethynyl-2′-deoxyuridine (EDU) to form [18F]FLETT was performed using an iPhase FlexLab module. The implementation of a vacuum distillation method afforded [18F]2-fluoroethyl azide in 87±5.3% radiochemical yield. The use of Cu(CH3CN)4PF6 and TBTA as catalyst enabled us to fully automate the [18F]FLETT synthesis without the need for the operator to enter the radiation field. [18F]FLETT was produced in higher overall yield (41.3±6.5%) and shorter synthesis time (67 min) than with our previously reported manual method (32.5±2.5% in 130 min). - Highlights: • An automated vacuum distillation method for the purification of [18F]2-fluoroethyl azide. • Significantly shortened synthesis protocol. • Increased yield and higher specific activity

  7. 18F-fluoromethylcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A literature revision

    Introduction: The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of 18 F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC). Materials and methods: A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed. Results: FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC). Conclusions: In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential. Advances in knowledge and implication for patient care: FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed

  8. Biodistribution and PET imaging of [{sup 18}F]-fluoroadenosine derivatives

    Alauddin, Mian M. [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States)]. E-mail: alauddin@di.mdacc.tmc.edu; Shahinian, Antranik [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States); Park, Ryan [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States); Tohme, Michael [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States); Fissekis, John D. [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States); Conti, Peter S. [Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles, CA 90033 (United States)

    2007-04-15

    Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl-adenine ([{sup 18}F]-FAA) and 3'-deoxy-3'-[{sup 18}F]fluoro-1-{beta}-D-xylofuranosyl-adenine ([{sup 18}F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [{sup 18}F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [{sup 18}F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [{sup 18}F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [{sup 18}F]FAA in spleen and visualization of tumors, and high uptake of [{sup 18}F]FXA in the heart. Conclusion: These results suggest that [{sup 18}F]FAA may be useful for tumor imaging, while [{sup 18}F]FXA may have potential as a heart imaging agent with PET.

  9. Interactions of 16α-[18F]-fluoroestradiol (FES) with sex steroid binding protein (SBP)

    Fluorine-18 16α-Fluoroestradiol ([18F]- FES) is a positron-emitting tracer for the estrogen receptor that is used for positron emission tomography (PET) studies of tumor tissues rich in the estrogen receptor. The role of the sex steroid binding protein (SBP or SHBG) in the transport of the [18F]-FES to the estrogen-receptor-rich tissue in breast cancer patients in vivo was investigated. To determine the extent to which [18F]-FES is bound to SBP in the blood, we performed a series of studies using blood samples obtained from patients undergoing [18F]-FES PET scans. The binding of [18F]-FES to the SBP was measured using a simple protein precipitation assay. The binding of [18F]-FES metabolites to SBP was also measured. These measurements showed that the tracer was distributed between albumin and SBP, and the binding capacity of SBP was sufficient to ensure that the protein was not saturated when the tracer was fully mixed with the plasma; however, local saturation of SBP may occur when [18F]-FES is administered intravenously. Typically about 45% of [18F]-FES in circulating plasma was bound to SBP, but this fraction was dependent on the concentration of SBP in plasma. The transfer of the tracer between the two proteins was rapid, complete in less than 20 s at 0 deg. C, suggesting that the equilibrium was maintained under most circumstances and that local saturation resolved quickly when blood from the injection site entered the central circulation. These data suggest that SBP binding of [18F]-FES is significant and will affect the input function of the tracer for any model that is used for the quantitative evaluation of [18F]-FES uptake in PET studies. Estimates of equilibrium binding in blood samples are sufficient to characterize [18F]-FES binding to SBP in the circulation

  10. <