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Sample records for carbon-11 methionine pet

  1. Brady-tachycardia syndrome after radiotherapy for lung cancer. Assessment by computed tomography and carbon-11 methionine positron emission tomography

    International Nuclear Information System (INIS)

    A 74-year-old male who had received radiotherapy (total 54 Gy) for right lung cancer 7 months earlier developed a symptomatic brady-tachycardia syndrome requiring the implantation of a permanent pacemaker. Chest CT showed a pulmonary tumor of 2-cm diameter in the right lower lobe with direct extension into the surrounding tissue, suggesting the possibility of cardiac invasion. Carbon-11 methionine positron emission tomography (PET) indicated the absence of visible invasion of the heart with lung cancer. The brady-tachycardia syndrome, therefore, was considered to be associated with sinus node injury due to radiation. Carbon-11 methionine PET metabolic imaging might play an important role in evaluating noninvasively the cause of the arrhythmia in this patient. (author)

  2. Radiation dose estimates for carbon-11-labelled PET tracers

    International Nuclear Information System (INIS)

    Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines. Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers. Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers. Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

  3. Carbon-11 acetate PET in recurrent prostate cancer

    International Nuclear Information System (INIS)

    Aim: Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) is not widely used for imaging of prostate cancer because of poor sensitivity. Thus, we evaluated C-11 acetate (AC-PET) in patients with PSA-recurrence and compared the findings to those of FDG-PET. Materials and Methods: We studied 46 patients with recurrent prostate cancer manifested by a detectable or rising PSA level following definitive treatment by prostatectomy or radiation therapy. After administration of 30 mCi (1110 MBq) C-11 acetate, PET images beginning in the pelvis and moving to the abdomen and chest were obtained over 35 min with an EXACT HR+ tomograph. After a suitable interval for radioactive decay, a Foley catheter was placed, 15 mCi (555 MBq) F-18 FDG was administered followed by furosemide injection, and images of the same regions were obtained 40 - 90 min later. The studies were then interpreted independently by 2 observers with correlation to biopsy, CT and bone scintigraphy when available. Results: The PSA level at the time of imaging ranged from 0.3 to 47.5 ng/mL (mean 5.2 ng/mL). Twenty-nine (63%) of patients had positive findings by AC-PET while only 8 (17%) were positive by FDG-PET. Disease confirmed by an abnormal prostate fossa biopsy, lymph nodes on CT or abnormal bone scintigraphy was present in 14 (30%) of patients imaged by AC-PET but only 4 (9%) of FDG-PET studies. No patient was positive by FDG-PET finding who was not also abnormal by AC-PET. Among the 22 patients with PSA > 3 ng/mL, 13 (59%) had abnormal AC-PET while only 1 of 24 (4%) with PSA less than or equal to 3 ng/mL were AC-PET positive. Conclusions: AC-PET is abnormal much more frequently than FDG-PET in patients with PSA recurrence, with most of the positive studies in patients with PSA > 3 ng/mL. Thus, AC-PET holds promise in imaging patients with recurrent prostate cancer

  4. Carbon-11-labeled daunorubicin and verapamil for probing P-glycoprotein in tumors with PET

    NARCIS (Netherlands)

    Elsinga, PH; Franssen, EJF; Hendrikse, NH; Fluks, L; Weemaes, AMA; vanderGraaf, WTA; deVries, GE; Visser, GM; Vaalburg, W

    1996-01-01

    One of the mechanisms for multidrug resistance (MDR) of tumors is an overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin and the modulator verapamil were labeled with C-11 to probe P-gp with PET. Methods: Carbon-11-daunorubicin was prepared from (CCH2N2)-C-11 with an aldeh

  5. Usefulness of {sup 11}C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Chung, J.-K.; Lee, Y.J.; Jeong, J.M. [Department of Nuclear Medicine, Seoul National University Hospital (Korea); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea); Kim, Y.K.; Kim, S.; Yeo, J.S.; Lee, D.S.; Lee, M.C. [Department of Nuclear Medicine, Seoul National University Hospital (Korea); Paek, S.; Jung, H.W. [Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea)

    2002-02-01

    The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. {sup 11}C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of {sup 11}C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased {sup 11}C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal {sup 11}C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased {sup 11}C-methionine uptake, the extent and degree of which exceeded {sup 18}F-FDG uptake, and the {sup 11}C-methionine uptake correlated with the proliferation index (r=0.67). The mean ({+-}SD) uptake ratios of glioma to normal brain on FDG and {sup 11}C-methionine PET were 0.92{+-}0.34 and 2.54{+-}1.25, respectively. All metastatic tumors except one showed intense {sup 11}C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, {sup 11}C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo

  6. {sup 11}C-methionine uptake in cerebrovascular disease. A comparison with {sup 18}F-FDG PET and {sup 99m}Tc-HMPAO SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Makoto; Kuwabara, Yasuo; Sasaki, Masayuki; Koga, Hirofumi; Chen, Tao; Kaneko, Kouichirou; Hayashi, Kazutaka; Morioka, Takato; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences

    2002-05-01

    Carbon-11-L-methyl-methionine ({sup 11}C-methionine) has been reported to be useful for evaluating brain tumors, but several other brain disorders have also shown signs of high methionine uptake. We retrospectively evaluated the significance of {sup 11}C-methionine uptake in cerebrovascular diseases, and also compared our results with those for {sup 18}F-FDG PET and {sup 99m}Tc-hexamethyl-propylene amine oxime (HMPAO) SPECT. Seven patients, including 3 patients with a cerebral hematoma and 4 patients with a cerebral infarction, were examined. All 7 patients underwent both {sup 11}C-methionine PET and {sup 99m}Tc-HMPAO SPECT, and 6 of them underwent {sup 18}F-FDG PET. A high {sup 11}C-methionine uptake was observed in all 3 patients with cerebral hematoma. Increased {sup 99m}Tc-HMPAO uptake was observed in 2 out of 3 patients, and all 3 patients had decreased {sup 18}F-FDG uptake. Of 4 patients with a cerebral infarction, high {sup 11}C-methionine uptake was observed in 3. Increased {sup 99m}Tc-HMPAO uptake was also observed in one patient, whereas 3 patients had decreased {sup 18}F-FDG uptake. We should keep in mind that high {sup 11}C-methionine uptake is frequently observed in cerebrovascular diseases. CVD should therefore be included in the differential diagnosis when encounting patients with a high {sup 11}C-methionine uptake. (author)

  7. Synthesis of n.c.a. PET-radiotracers with carbon-11

    International Nuclear Information System (INIS)

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. 11C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1-11C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1-11C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [11C]CO2 with a radiochemical yield (RCY) of 68 ± 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals (Rc) in humans, [1-11C]acetylsalicylic acid, acetyl-[carboxy-11C]salicylic acid and [carboxy-11C]salicylic acid were prepared. N.c.a. [1-11C]acetylsalicylic acid was synthesized via the reaction of [1-11C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 ± 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy-11C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [11C]CO2. Best results (87 ± 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy-11C]salicylic acid to acetyl-[carboxy-11C]salicylic acid was performed using acetylchloride in CH2Cl2 with a radiochemical yield of 65 ± 4%. (orig.)

  8. Evaluation glioma for C-11-methyl-L-methionine PET

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) using a positron tracer allows noninvasive measurement of regional brain metabolism and has been utilized for pathophysiological evaluation of brain tumors and as a highly specific means for diagnosis of brain tumors. Like the images yielded from anatomical imaging techniques such as computer tomography (CT) and magnetic resonance imaging (MRI), PET images play an important role as functional images. In cases of glioma, the manner by which the tumor cells spread to surrounding cells varies from case to case, and the extent of their spread also varies among different cases. It is reported that glioma is difficult to detect on anatomical images. C-11-methyl-L-methionine (Met) is taken up into glioma more markedly than into intact tissue and is thus considered to provide a useful means of tumor localization. It is possible to precisely determine the scope of glioma invasion by CT, MRI or F-18 fluoro-2-deoxy-D-glucose (FDG)-PET. This information is useful in determining an optimal operative procedure, the scope of postoperative radiotherapy and an optimal chemotherapy individual cases. It is also known that the evaluation of the malignancy level of glioma is closely related to the prognosis of patients with this tumor. Although FDG-PET allows evaluation of the malignancy level of glioma, PET using methionine (Met-PET) provides the best means of localization of tumors (including determination of the extent of tumor invasion). Therefore, if a technique of evaluating the malignancy level of glioma using Met-PET is established, it will be highly useful in clinical practice. At our facility, attempts have been made to use FDG-PET and Met-PET for evaluation of the malignancy level and scope of invasion of tumors in patients suspected of having brain tumors. The present study was undertaken to evaluate the degree of accumulation of Met in glioma using Met-PET (a technique expected to allow more accurate evaluation of the extent of tumor

  9. Synthesis of n. c. a. PET-radiotracers with carbon-11. Zur Synthese traegerarme PET-Radiotracer mit Kohlenstoff-11

    Energy Technology Data Exchange (ETDEWEB)

    Schirbel, A.

    1998-11-01

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. [sup 11]C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1-[sup 11]C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1-[sup 11]C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [[sup 11]C]CO[sub 2] with a radiochemical yield (RCY) of 68 [+-] 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals (<20 min). In order to study the pharmacokinetics and metabolism of acetylsalicylic acid (Aspirin[sup R]c) in humans, [1-[sup 11]C]acetylsalicylic acid, acetyl-[carboxy-[sup 11]C]salicylic acid and [carboxy-[sup 11]C]salicylic acid were prepared. N.c.a. [1-[sup 11]C]acetylsalicylic acid was synthesized via the reaction of [1-[sup 11]C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 [+-] 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy-[sup 11]C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [[sup 11]C]CO[sub 2]. Best results (87 [+-] 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy-[sup 11]C]salicylic acid to acetyl-[carboxy-[sup 11]C]salicylic acid was performed using acetylchloride in CH[sub 2]Cl[sub 2] with a radiochemical yield of 65 [+-] 4%. (orig.)

  10. Utility of “1”1C -methionine PET/CT in neuro-oncology

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) with “1”1C-methionine (“1”1C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and “1”1C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and “1”1C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of “1”1C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike “1”8fluordeoxiglucose PET/TC, “1”1C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The “1”1C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. “1”1C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas. (authors)

  11. Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer

    International Nuclear Information System (INIS)

    Purpose: To demonstrate the theoretical feasibility of [11C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL's) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). Methods and materials: Twelve men with intracapsular prostate carcinoma were imaged with [11C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIBIMRT) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. Results: [11C]Acetate was used to delineate the IPL's of all 12 patients. With every patient the TCP was increased with SIBIMRT without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIBIMRT treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. Conclusions: Our study indicates that [11C]acetate can be used to define the IPL's and in combination with SIBIMRT the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [11C]acetate PET for biological dose planning in prostate cancer.

  12. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D2 receptors.

    Science.gov (United States)

    Langer, O; Halldin, C; Dollé, F; Swahn, C G; Olsson, H; Karlsson, P; Hall, H; Sandell, J; Lundkvist, C; Vaufrey, F; Loc'h, C; Crouzel, C; Mazière, B; Farde, L

    1999-07-01

    Epidepride [(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenza mide] binds with a picomolar affinity (Ki = 24 pM) to the dopamine D2 receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D2 receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [11C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/micromol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [11C]epidepride binding. The fraction of unchanged [11C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [11C]epidepride. The availability of [11C]epidepride allows the PET-verification of the data obtained from quantitation studies with SPECT. PMID:10473189

  13. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D2 receptors

    International Nuclear Information System (INIS)

    Epidepride {(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide} binds with a picomolar affinity (Ki=24 pM) to the dopamine D2 receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D2 receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [11C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/μmol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [11C]epidepride binding. The fraction of unchanged [11C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [11C]epidepride. The availability of [11C]epidepride allows the PET-verification of the data obtained from quantitation studies with SPECT.

  14. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

    1999-07-01

    Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

  15. Development of rapid multistep carbon-11 radiosynthesis of the myeloperoxidase inhibitor AZD3241 to assess brain exposure by PET microdosing

    International Nuclear Information System (INIS)

    Introduction: The myeloperoxidase inhibitor AZD3241 has been selected as a candidate drug currently being developed to delay progression in patients with neurodegenerative brain disorders. Part of the decision tree for translation of AZD3241 into clinical studies included the need for assessment of brain exposure in non-human primates by PET microdosing. For that purpose a rapid multistep method for 11C-labeling of AZD3241 was developed. Methods: AZD3241 was labeled in the thio-carbonyl position starting from [11C]potassium cyanide in a 4-step procedure using microwave assisted heating. In the first step [11C]potassium cyanide was converted to [11C]potassium thiocyanate followed by reaction with benzoyl chloride to yield benzoyl [11C]isothiocyanate. The benzoyl [11C]isothiocyanate was subsequently reacted with the precursor ethyl 3-(2-isopropoxyethylamino)-1H-pyrrole-2-carboxylate and the formed intermediate underwent a base catalyzed cyclization to obtain [11C]AZD3241 in the final step. To assess [11C]AZD3241 brain exposure PET measurements were performed in three cynomolgus monkeys. Results: [11C]AZD3241 was produced in good and reproducible radiochemical yield 710 ± 294 MBq (mean ± SD, n = 7). Total time of synthesis was 60 min from end of bombardment. The specific radioactivity was 9 ± 4 GBq/μmol and the radiochemical purity was > 98%. Following iv administration of [11C]AZD3241 there was a rapid presence of radioactivity in brain in each of the three monkeys. The distribution of [11C]AZD3241 to brain was fast and a Cmax of 1.9 to 2.6% of the injected radioactivity was observed within 1.5 min. [11C]AZD3241 was homogeneously distributed in brain. Conclusion: The MPO inhibitor AZD3241 was successfully labeled with carbon-11 in a challenging 4-step procedure in good radiochemical yield allowing PET microdosing studies in cynomolgus monkey. [11C]AZD3241 rapidly entered brain and confirmed adequate brain exposure to support translation of AZD3241 to phase 2a

  16. Usefulness of 11C-methionine PET in evaluation of brain lesions with hypo- or isometabolism on 18F-FDG PET

    International Nuclear Information System (INIS)

    Because some brain tumors show iso-or hypometabolism on 18F-FDG PET, there have been problems in detection of primary or recurrent tumor and in differentiation from benign lesion with 18F-FDG PET. We investigated the usefulness of 11C-methionine PET in characterizing brain lesions in these conditions. In 34 patients with brain lesions (27 for initial diagnosis, 7 for detecting recurrence ) who showed hypo- or isometabolism compared to normal brain tissue on 18F-FDG PET, we performed 11C-methionine PET. Five minutes after injection of 550 MBq 11C-methionine, attenuation corrected brain images were obtained with a dedicated PET scanner. Brain lesions were 18 gliomas, 4 metastatic brain tumors, 2 meningiomas, 1 mixed germ cell tumor and 3 benign tumors and 6 non-tumorous lesions (3 neurocysticercosis, 2 meningiomas, 1 mixed germ cell tumor and 3 benign tumors and 6 non-tumorous lesions (3 neurocysticercosis, 2 tumor necrosis, 1 granuloma). To find the correlation between methione uptake and proliferation activity, Ki 67 proliferation Index in 8 patients or Proliferation index (P1=G2+M+S/total cycle) using DNA flow cytometry in 10 patients were obtained. Of 25 tumorous lesions without definitive hypermetabolism on 18F-FDG PET, all except two glioma (92%) showed moderate to high uptake in entire or thick peripheral tumor uptake in 11C-methionine PET. The uptake ratio of tumor to normal brain in 18F-FDG and 11C-methionine PET were 0.96 ±0.32 and 2.43 ± 1.26, respectively. Nine benign lesions with hypo- or isometabolism on 18F-FDG PET were also no significantly increased 11C-methionine uptake. 11C-methionine uptake and proliferation activity were correlated with Ki 67 index or PI (r=0.6). Two glioma shown no increased 11C-methionine uptake had low proliferative activity (Ki 67 11C-methionin PET could detect brain tumors and differentiate brain lesions with high sensitivity and good contrast, which showed iso- or hypometabolism on 18F-FDG PET. In evaluation of these

  17. Usefulness of {sup 11}C-methionine PET in evaluation of brain lesions with hypo- or isometabolism on {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Y. K.; Chung, J. K.; Yeo, J. S.; Lee, D. S.; Jeong, H. W.; Lee, M. C. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2000-07-01

    Because some brain tumors show iso-or hypometabolism on {sup 18}F-FDG PET, there have been problems in detection of primary or recurrent tumor and in differentiation from benign lesion with {sup 18}F-FDG PET. We investigated the usefulness of {sup 11}C-methionine PET in characterizing brain lesions in these conditions. In 34 patients with brain lesions (27 for initial diagnosis, 7 for detecting recurrence ) who showed hypo- or isometabolism compared to normal brain tissue on {sup 18}F-FDG PET, we performed {sup 11}C-methionine PET. Five minutes after injection of 550 MBq {sup 11}C-methionine, attenuation corrected brain images were obtained with a dedicated PET scanner. Brain lesions were 18 gliomas, 4 metastatic brain tumors, 2 meningiomas, 1 mixed germ cell tumor and 3 benign tumors and 6 non-tumorous lesions (3 neurocysticercosis, 2 meningiomas, 1 mixed germ cell tumor and 3 benign tumors and 6 non-tumorous lesions (3 neurocysticercosis, 2 tumor necrosis, 1 granuloma). To find the correlation between methione uptake and proliferation activity, Ki 67 proliferation Index in 8 patients or Proliferation index (P1=G2+M+S/total cycle) using DNA flow cytometry in 10 patients were obtained. Of 25 tumorous lesions without definitive hypermetabolism on {sup 18}F-FDG PET, all except two glioma (92%) showed moderate to high uptake in entire or thick peripheral tumor uptake in {sup 11}C-methionine PET. The uptake ratio of tumor to normal brain in {sup 18}F-FDG and {sup 11}C-methionine PET were 0.96 {+-}0.32 and 2.43 {+-} 1.26, respectively. Nine benign lesions with hypo- or isometabolism on {sup 18}F-FDG PET were also no significantly increased {sup 11}C-methionine uptake. {sup 11}C-methionine uptake and proliferation activity were correlated with Ki 67 index or PI (r=0.6). Two glioma shown no increased {sup 11}C-methionine uptake had low proliferative activity (Ki 67 < 1%). {sup 11}C-methionin PET could detect brain tumors and differentiate brain lesions with high

  18. Pre-operative localisation of hyperfunctional parathyroid tissue with {sup 11}C-methionine PET

    Energy Technology Data Exchange (ETDEWEB)

    Otto, D.; Boerner, A.R.; Hofmann, M.; Brunkhorst, T.; Meyer, G.J.; Petrich, T.; Knapp, W.H. [Hannover University Medical School, Department of Nuclear Medicine, Hannover (Germany); Scheumann, G.F. [Hannover University Medical School, Department of Visceral and Transplant Surgery, Hannover (Germany)

    2004-10-01

    Previous studies have shown high sensitivity of positron emission tomography (PET) with {sup 11}C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of {sup 11}C-methionine PET and {sup 99m}Tc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of {sup 11}C-methionine in those patients with inconclusive or negative conventional imaging. Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with {sup 99m}Tc-MIBI and PET with {sup 11}C-methionine. SUV{sub parathyroid}/SUV{sub cervical} {sub soft} {sub tissue} (target-to-background) and SUV{sub parathyroid} {sub tissue}/SUV{sub thyroid} {sub tissue} (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one. In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with {sup 11}C-methionine PET and 17 (47%) with {sup 99m}Tc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. {sup 99m}Tc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with {sup 99m}Tc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non

  19. Clinical impact of 11C-methionine PET on expected management of patients with brain neoplasm

    International Nuclear Information System (INIS)

    We retrospectively examined the clinical efficacy of 11C-methionine positron emission tomography (11C-MET PET) in patients with brain neoplasm, especially whether the 11C-MET PET changed the clinical management and whether the change was beneficial or detrimental. This study reviewed 89 11C-MET PET scans for 80 patients (20 scans for initial diagnosis of brain tumor and 69 scans for differentiating tumor recurrence from radiation necrosis). Final diagnosis and the effect on the intended management were obtained from the questionnaire to the referring physicians or directly from the medical records. The diagnostic sensitivity, specificity, and accuracy for the 11C-MET PET were evaluated. Regarding the management impact, the rate of scans that caused changes in intended management was also evaluated. Moreover, the occurrence of scans having detrimental diagnostic impact (DDI) and beneficial diagnostic impact (BDI) were evaluated. Sensitivity, specificity, and accuracy of 11C-MET PET was 87.8, 80.0, and 85.9%. The intended management was changed in 50.0% of the scans. DDI and BDI were observed in 4.3 and 36.2% of the total relevant scans, respectively. 11C-MET PET can provide useful information in initial diagnosis and differentiating tumor recurrence from radiation necrosis. The intended management was changed in half of the scans. Since a few cases did not receive the requisite treatment due to false-negative results of 11C-MET PET, management decision should be made carefully, especially in the case of a negative scan. (orig.)

  20. Volumetry of [11C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme

    OpenAIRE

    Galldiks, Norbert; Ullrich, Roland; Schroeter, Michael; Fink, Gereon R.; Kracht, Lutz W.

    2009-01-01

    Purpose We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [11C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM). Material and methods MET-PET and contrast-enhanced MRI with Gd-DTPA were performed in 12 uniformly pretreated patients wit...

  1. Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ohtani, Toshiyuki; Kurihara, Hideyuki; Ishiuchi, Shogo; Saito, Nobuhito; Sasaki, Tomio [Dept. of Neurosurgery, Gunma University School of Medicine (Japan); Oriuchi, Noboru; Inoue, Tomio [Dept. of Nuclear Medicine, Gunma University School of Medicine, Maebashi (Japan)

    2001-11-01

    The purpose of this study was to assess the clinical potential of methyl-{sup 11}C-choline ({sup 11}C-choline) in the diagnosis of brain tumours. To this end, the results of {sup 11}C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of {sup 11}C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of {sup 11}C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean{+-}SD: 8.7{+-}6.2, n=9 versus 1.5{+-}0.7, n=5, P<0.03) when data pertaining to the prominent uptake of {sup 11}C-choline in a patient with a pilocytic astrocytoma were excluded. {sup 11}C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of {sup 11}C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. {sup 11}C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of {sup 11}C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas. (orig.)

  2. Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean±SD: 8.7±6.2, n=9 versus 1.5±0.7, n=5, P11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas. (orig.)

  3. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET

    International Nuclear Information System (INIS)

    The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using 11CO2 and the appropriate Grignard reagents. [11C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity were the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low ( VPA > PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [11C]BA showed relatively high uptake in spleen and pancreas whereas [11C]PBA showed high uptake in liver and heart. Notably, [11C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects

  4. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[11C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [11C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [11C]CH3OTf through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [11C]CO2, were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  5. Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluation

    International Nuclear Information System (INIS)

    Papaverine, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, a specific inhibitor of phosphodiesterase (PDE) 10A with IC50 values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A. Here, we report the radiosynthesis of [11C]papaverine and the in vitro and in vivo evaluation of [11C]papaverine as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of papaverine with 11C was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]papaverine was obtained with ∼70% radiochemical yield and a specific activity >10 Ci/μmol. In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of [11C]papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of [11C]papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of [11C]papaverine from brain. Our initial evaluation suggests that despite papaverine's utility for in vitro studies and as a pharmaceutical tool, [11C]papaverine is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Analogs of papaverine having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

  6. Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: tuz@mir.wustl.edu; Xu Jinbin; Jones, Lynne A.; Li Shihong; Mach, Robert H. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2010-05-15

    Papaverine, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, a specific inhibitor of phosphodiesterase (PDE) 10A with IC{sub 50} values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A. Here, we report the radiosynthesis of [{sup 11}C]papaverine and the in vitro and in vivo evaluation of [{sup 11}C]papaverine as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of papaverine with {sup 11}C was achieved by O-methylation of the corresponding des-methyl precursor with [{sup 11}C]methyl iodide. [{sup 11}C]papaverine was obtained with {approx}70% radiochemical yield and a specific activity >10 Ci/{mu}mol. In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of [{sup 11}C]papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of [{sup 11}C]papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of [{sup 11}C]papaverine from brain. Our initial evaluation suggests that despite papaverine's utility for in vitro studies and as a pharmaceutical tool, [{sup 11}C]papaverine is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Analogs of papaverine having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

  7. Further evaluation of the carbon11-labelled D2/3 agonist PET radiotracer PHNO: reproducibility in tracer characteristics and characterization of extrastriatal binding

    Science.gov (United States)

    Egerton, Alice; Hirani, Ella; Ahmad, Rabia; Turton, David R; Brickute, Diana; Rosso, Lula; Howes, Oliver D; Luthra, Sajinder K; Grasby, Paul M

    2014-01-01

    [11C]-(+)-PHNO is a new dopamine D2/3 receptor agonist radiotracer which has been successfully used to measure D2/3 receptor availability in experimental animals and man. Here we report in vivo evaluation in the rat of the biodistribution, metabolism, specificity, selectivity and dopamine sensitivity of carbon-11 labeled PHNO ([11C]-3-PHNO) produced by an alternative radiochemical synthesis method. [11C]-3-PHNO showed rapid metabolism and clearance from most peripheral organs and tissues. [11C]-3-PHNO, but not its polar metabolite, readily crossed the blood-brain barrier and showed high levels of uptake in the D2/3 -rich striatum. Pre-treatment with unlabelled PHNO and the D2/3 receptor antagonist raclopride indicated that binding in the striatum was specific and selective to D2/3 receptors. PET studies in anaesthetized rats revealed significant reductions in [11C]-3-PHNO binding in the striatum following amphetamine administration, indicating sensitivity to increases in endogenous dopamine concentrations. D2/3 antagonist pre-treatment additionally indicated moderate levels of [11C]-3-PHNO specific binding in several extrastriatal brain areas – most notably the olfactory bulbs and tubercles, thalamus and hypothalamus. Of particular interest, approximately 30% of [11C]-3-PHNO signal in the cerebellum – a region often used as a ‘low-binding’ reference region for PET quantification - was attributable to specific signal. These data demonstrate that [11C]-3-PHNO shows similar tracer characteristics to [11C]-(+)-PHNO, but additionally indicate that radiolabeled PHNO may be used to estimate D2/3 receptor availability in select extrastriatal brain regions with PET. PMID:19957364

  8. Comparative evaluation of 11C methionine (MET-PET) and 18F flurodeoxyglucose (FDG) PET/CT for detection of recurrent brain tumors

    International Nuclear Information System (INIS)

    Full text: Comparative evaluation of 11C Methionine (MET-PET) and 18F flurodeoxyglucose (FDG) PET/CT for detection of recurrent brain tumors. Patients and Methods: 23 post-operative, histologically proven cases of primary brain tumors were included; there were two cases of grade I (WHO), 9 cases of grade II, 5 cases of grade III, 3 cases of grade IV, 3 medulloblastomas and one gliosarcoma. Ratio of M:F=16:7, age 27.5+14.4 years (range 5-56 years). All patients underwent the MET-PET and FDG-PET scans on the same day. Images were evaluated for recurrence using visual analysis and final results were compared with MRI/MRS and follow up as gold standard. Results: Fourteen cases were positive for recurrence on the MET-PET study while FDG was unequivocally positive in eleven cases. MET-PET scans were true negative for recurrence in nine cases and concurrent with the MRI/MRS findings in all 23 cases. Tumor to background ratio for the MET-PET study were 2.2+.55. Conclusion: MET-PET is superior to FDG-PET for detection of recurrence in both low and high grade gliomas and has excellent correlation with MRI/MRS

  9. Prognostic value of volume-based measurements on 11C-methionine PET in glioma patients

    International Nuclear Information System (INIS)

    11C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach

  10. Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes

    International Nuclear Information System (INIS)

    Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[11C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([11C]8) and (3aR,9bS)-1-[11C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([11C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [11C]CH3OTf through N-[11C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/μmol specific activity at EOB

  11. Uptake of 11C-methionine in breast cancer studied by PET. An association with the size of S-phase fraction.

    OpenAIRE

    Leskinen-Kallio, S.; Någren, K.; Lehikoinen, P.; Ruotsalainen, U; Joensuu, H

    1991-01-01

    L-[methyl-11-C]methionine (11C-methionine) uptake of seven primary breast cancers, four soft tissue metastases of breast cancer, and three other breast lesions was studied by positron emission tomography (PET). 11C-methionine accumulation was assessed by calculating the standardised uptake value (SUV). The mean SUV for breast cancer was 8.5 +/- 3.3 (s.d.), while the maximal uptake in the liver was 12.4 +/- 1.6, in the bone marrow 5.8 +/- 0.7, and in the myocardium 3.4 +/- 0.6. All eight malig...

  12. A False-Negative Case of Primary Central Nervous System Lymphoma on 11C-Methionine PET and Intense 18F-FDG Uptake.

    Science.gov (United States)

    García-Garzon, J R; Villasboas-Rosciolesi, Diego; Baquero, Miguel; Bassa, Pere; Soler, Marina; Riera, Eduard

    2016-08-01

    We report a case of a 44-year-old man with neurological symptoms and MRI findings, which were unable to differentiate between glioma and lymphoma. Metabolic characterization by means of PET imaging with F-FDG and C-methionine is proposed to determine the benign or tumor (high- and low-grade) origin of brain lesions. In this case, the MRI lesion corresponded with an inconclusive metabolic pattern of intense F-FDG uptake and no significant C-methionine uptake. Pathological study revealed a false-negative case of C-methionine due to lymphoma. PMID:27187734

  13. Tracers development for the PET study of nicotinic receptors: [11C]-mecamylamine and [11C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PAstop

    International Nuclear Information System (INIS)

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [11C]-t-PAstop and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [11C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[11C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [11C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [11C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [11C]-SIB 1553A, a selective agonist for the nicotinic β4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[11C]-methylation reaction (yield: 75%). The [11C]-t-PAstop was obtained from [11C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PAstop did not permit to obtain the [3H]-t-PAstop but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  14. Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    International Nuclear Information System (INIS)

    We evaluated whether the dynamic profile of L-11C-methionine (11C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic 11C-MET PET was performed by small animal PET up to 120 min after injection of 11C-MET. The next day, after overnight fasting, the rats were injected with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG), and dynamic 18F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. 11C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11C-MET uptake in the granuloma was significantly different from that in the tumor (p 11C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 ± 0.09) was significantly lower than that in the tumor (1.72 ± 0.18, p 18F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic 11C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  15. Dynamic {sup 11}C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Songji; Zhao, Yan [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji; Hatano, Toshiyuki [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Yi, Min; Kohanawa, Masashi [Hokkaido University, Department of Advanced Medicine, Graduate School of Medicine, Sapporo (Japan); Magota, Keiichi; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Nishijima, Ken-ichi [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan)

    2011-10-15

    We evaluated whether the dynamic profile of L-{sup 11}C-methionine ({sup 11}C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic {sup 11}C-MET PET was performed by small animal PET up to 120 min after injection of {sup 11}C-MET. The next day, after overnight fasting, the rats were injected with {sup 18}F-2-deoxy-2-fluoro-D-glucose ({sup 18}F-FDG), and dynamic {sup 18}F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. {sup 11}C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of {sup 11}C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of {sup 11}C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 {+-} 0.09) was significantly lower than that in the tumor (1.72 {+-} 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of {sup 18}F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic {sup 11}C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  16. Clinical value of {sup 11}C-methionine PET/CT in patients with plasma cell malignancy: comparison with {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, Yuji; Kurihara, Kensuke; Nakatani, Koya; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, Kyoto (Japan); Nishizawa, Masatoshi; Yamashita, Kouhei; Kondo, Tadakazu; Takaori-Kondo, Akifumi [Kyoto University Graduate School of Medicine, Department of Hematology and Oncology, Kyoto (Japan)

    2013-05-15

    PET/CT using FDG has been widely used for the imaging of various malignant tumours, including plasma cell malignancy (PCM), but {sup 11}C-methionine (MET), as a radiolabelled amino acid tracer, may also be useful because PCM is able to activate protein synthesis. The purpose of this study was to evaluate the clinical value of PET/CT imaging using MET in PCM, including multiple myeloma, compared with that of FDG PET/CT. The study group comprised 20 patients with histologically proven PCM who underwent FDG PET/CT and MET PET/CT scans before (n = 6) or after (n = 14) treatment. Semiquantitative analysis was performed on a lesion basis. We also visually evaluated the scans qualitatively using a five-point scale (0, negative; 1, probably negative; 2, equivocal; 3, probably positive; 4, positive) on a lesion and a patient basis. The results were compared between the two scans. Active PCM was confirmed in 15 patients, including two patients with extramedullary lesions. Uptake of MET tended to be higher (maximum standardized uptake value 10.3 {+-} 5.6, mean {+-} SD) than that of FDG (3.4 {+-} 2.7, p < 0.001), and more lesions of grade 3 or 4 were depicted by MET (MET 156 lesions vs. FDG 58 lesions). On a patient basis, two patients were accurately diagnosed only by MET. In the remaining 18 patients, consistent results were obtained, but potential upgrade of staging or restaging was necessary in 6 of 11 positive patients because more abnormal lesions were demonstrated by MET. The patient-based sensitivity, specificity and accuracy of MET for restaging were 89 %, 100 % and 93 %, respectively, while those of FDG were 78 %, 100 % and 86 %, respectively. MET revealed an equal or greater number of lesions in PCM than FDG. MET may be especially useful when negative or inconclusive findings are obtained by FDG despite highly suspicious indications of recurrence. (orig.)

  17. Clinical value of 11C-methionine PET/CT in patients with plasma cell malignancy: comparison with 18F-FDG PET/CT

    International Nuclear Information System (INIS)

    PET/CT using FDG has been widely used for the imaging of various malignant tumours, including plasma cell malignancy (PCM), but 11C-methionine (MET), as a radiolabelled amino acid tracer, may also be useful because PCM is able to activate protein synthesis. The purpose of this study was to evaluate the clinical value of PET/CT imaging using MET in PCM, including multiple myeloma, compared with that of FDG PET/CT. The study group comprised 20 patients with histologically proven PCM who underwent FDG PET/CT and MET PET/CT scans before (n = 6) or after (n = 14) treatment. Semiquantitative analysis was performed on a lesion basis. We also visually evaluated the scans qualitatively using a five-point scale (0, negative; 1, probably negative; 2, equivocal; 3, probably positive; 4, positive) on a lesion and a patient basis. The results were compared between the two scans. Active PCM was confirmed in 15 patients, including two patients with extramedullary lesions. Uptake of MET tended to be higher (maximum standardized uptake value 10.3 ± 5.6, mean ± SD) than that of FDG (3.4 ± 2.7, p < 0.001), and more lesions of grade 3 or 4 were depicted by MET (MET 156 lesions vs. FDG 58 lesions). On a patient basis, two patients were accurately diagnosed only by MET. In the remaining 18 patients, consistent results were obtained, but potential upgrade of staging or restaging was necessary in 6 of 11 positive patients because more abnormal lesions were demonstrated by MET. The patient-based sensitivity, specificity and accuracy of MET for restaging were 89 %, 100 % and 93 %, respectively, while those of FDG were 78 %, 100 % and 86 %, respectively. MET revealed an equal or greater number of lesions in PCM than FDG. MET may be especially useful when negative or inconclusive findings are obtained by FDG despite highly suspicious indications of recurrence. (orig.)

  18. Novel carbon-11 labeled 4-dimethylamino-but-2-enoic acid [4-(phenylamino)-quinazoline-6-yl]-amides: potential PET bioprobes for molecular imaging of EGFR-positive tumors

    International Nuclear Information System (INIS)

    We have previously reported of labeled reversible and irreversible EGFR inhibitors, such as 4-(3,4-dichloro-6-fluoroanilino)-6,7-dimethoxyquinazoline (ML01) and 6-acrylamido-4-(3,4-dichloro-6-fluoroanilino)quinazoline (ML03), to be suboptimal as imaging agents. On the basis of these studies, a new generation of novel, more chemically stable irreversible inhibitors was labeled with carbon-11 as potential positron emission tomography (PET) biomarkers for molecular imaging of epidermal growth factor receptor (EGFR)-positive tumors. In these new labeled, irreversible inhibitors the acryl-amide group at the 6-position of the quinazoline ring was replaced with a 4-dimethylamino-but-2-enoic amide. The nonlabeled compounds were evaluated in vitro to determine their EGFR autophosphorylation IC50 values. The IC50 values indicated that these new irreversible compounds possess similar potencies towards the EGFR, as the parent compound, ML03. These compounds were labeled with carbon-11 at the dimethylamine moiety, using the well known labeling reagent C-11 MeI. The labeling procedure was automated using a commercial module. The final products were obtained with 10% decay corrected radiochemical yield, 99% radiochemical purity, 96% chemical purity, and a high specific activity of 2.7 Ci/μmol EOB. The high potency of these new labeled bioprobes towards the EGFR establishes their potential to serve as PET agents for molecular imaging of EGFR-positive tumors

  19. Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM) is characterized by tissue hypoxia associated with resistance to radiotherapy and chemotherapy. To clarify the biological link between hypoxia and tumour-induced neovascularization and tumour aggressiveness, we analysed detailed volumetric and spatial information of viable hypoxic tissue assessed by 18F-fluoromisonidazole (FMISO) PET relative to neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl-11C-methionine (MET) PET in newly diagnosed GBMs. Ten patients with newly diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI before surgery. Tumour volumes were calculated by performing a three-dimensional threshold-based volume of interest (VOI) analysis for metabolically active volume on MET PET (MET uptake indices of ≥1.3 and ≥1.5) and Gd-enhanced volume on MRI. FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B) images. The hypoxic volume (HV) was defined as the region with T/B greater than 1.2. PET and MR images of each patient were coregistered to analyse the spatial location of viable hypoxic tissue relative to neovascularization and active tumour extension. Metabolically active tumour volumes defined using MET uptake indices of ≥1.3 and ≥1.5 and the volumes of Gd enhancement showed a strong correlation (r = 0.86, p < 0.01 for an index of ≥1.3 and r = 0.77, p < 0.05 for an index of ≥1.5). The HVs were also excellently correlated with the volumes of Gd enhancement (r = 0.94, p < 0.01). The metabolically active tumour volumes as defined by a MET uptake index of ≥1.3 and the HVs exhibited a strong correlation (r = 0.87, p < 0.01). On superimposed images, the metabolically active area on MET PET defined by a MET uptake index of ≥1.3 was usually larger than the area of the Gd enhancement and about 20-30% of the MET area extended outside the area of the enhancement. On the other hand, the surface area of viable hypoxic tissue with a T/B cutoff of

  20. Combined 18F-FDG and 11C-Methionine PET/CT scans in a case of metastatic hepatocellular carcinoma

    International Nuclear Information System (INIS)

    A 37-year-old male who underwent a central hepatectomy of the liver for hepatocellular carcinoma (HCC) was referred for an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study to rule out tumor recurrence or metastases. The scan showed a recurrent hepatic mass at the operative site, along with low-grade uptake in bilateral pulmonary metastases, mediastinal and hilar lymph nodes, and few skeletal sites. A non-FDG avid intracranial extradural mass was visualized in the right frontal lobe. The 11C-methionine PET/CT scan performed subsequently revealed a larger area of involvement at the primary site, along with widespread metastases to the lungs, mediastinal, hilar, and abdominal lymph nodes, and multiple skeletal sites. Further, dural metastasis with high tracer uptake was noted in the frontal region. To the best of our knowledge, this is the first case documented in the literature, wherein 11C-methionine PET/CT played a significant role in delineating the widespread dissemination, including the extremely rare dural involvement in a case of HCC. This report highlights the potential value of 11C-methionine PET/CT in assessing the hepatic and extrahepatic tumor burden in cases of HCC, especially in clinically unexpected locations

  1. Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme -insight form a PET and MR fusion images study

    International Nuclear Information System (INIS)

    Purpose: 11C-methyl methionine (MET) accumulation on positron emission tomography (PET) imaging of glioblastomaPmultiforme (GBM) was examined to determine the distribution of metabolic abnormality of this tumour. This distribution was compared with the abnormal tumour signal intensity of GBM on MRI to evaluate the discrepancy between lesion distributions yielded by these methods. Methods: MET-PET was performed for 10 patients with newly diagnosed GBM before treatment. At the same time, MRI was performed and superimposed on corresponding MET-PET images using a SUN workstation. The differences between the extended area of MET accumulation on PET imaging (MET area), that of the gadolinium (Gd)-enhanced area on T1-weighted images (Gd area), and that of the abnormal high signal intensity area on T2-weighted images (T2-high area) were assessed. Results: The MET area was distinctly larger than the Gd area and included the entire Gd area. The discrepancy in volume between the MET area and the Gd area became larger with increasing tumour diameter. On average, 58.6% of the MET area was located within the Gd area, 90.1% within 10 mm outside of the Gd area, 98.1% within 20 mm of the Gd area and 99.8% within 30 mm of the Gd area. A newly developed Gd area has emerged in 5 of the 10 cases in their clinical courses until the time of this study. The newly developed Gd area was demonstrated even in the MET area after completely surgical resection of Gd area in the initial MRI in 3 of the 5 cases, and originated in the residual Gd area after surgery in the remaining 2 cases. In all cases, the T2-high area was larger than the MET area. The MET area extended partly beyond the T2-high area in 9 cases, and the MET area was completely within the T2-high area in one case. Conclusion: Previous PET studies on GBM have reported that the MET area corresponds well with the area of tumour extension. The results of our study show that GBM cells may extend over the Gd area and more widely with

  2. Prognostic value of volume-based measurements on {sup 11}C-methionine PET in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kentaro; Manabe, Osamu; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Hirata, Kenji [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Yamaguchi, Shigeru; Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University, Department of Neurosurgery, Graduate School of Medicine, Sapporo (Japan); Hattori, Naoya [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan); Tanaka, Shinya [Hokkaido University, Department of Cancer Pathology, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2015-04-08

    {sup 11}C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not

  3. Volumetry of [11C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme

    International Nuclear Information System (INIS)

    We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [11C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM). MET-PET and contrast-enhanced MRI with Gd-DTPA were performed in 12 uniformly pretreated patients with recurrent GBM. To calculate the volumes in cubic centimetres, a threshold-based volume-of-interest (VOI) analysis of the metabolically active tumour volume (MET uptake indexes of ≥1.3 and ≥1.5) and of the area of Gd-DTPA enhancement was performed after coregistration of all images. In all patients, the metabolically active tumour volume as shown using a MET uptake index of ≥1.3 was larger than the volume of Gd-DTPA enhancement (30.2 ± 22.4 vs. 13.7 ± 10.6 cm3; p = 0.04). Metabolically active tumour volumes as shown using MET uptake indexes of ≥1.3 and ≥1.5 and the volumes of Gd-DTPA enhancement showed a positive correlation (r = 0.76, p = 0.003, for an index of ≥1.3, and r = 0.74, p = 0.005, for an index of ≥1.5). The present data suggest that in patients with recurrent GBM the metabolically active tumour volume may be substantially underestimated by Gd-DTPA enhancement. The findings support the notion that complementary information derived from MET uptake and Gd-DTPA enhancement may be helpful in developing individualized, patient-tailored therapy strategies in patients with recurrent GBM. (orig.)

  4. Volumetry of [{sup 11}C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Galldiks, Norbert; Schroeter, Michael; Fink, Gereon R. [University Hospital of Cologne, Department of Neurology, Cologne (Germany); Ullrich, Roland; Kracht, Lutz W. [Max Planck-Institute for Neurological Research, Cologne (Germany)

    2010-01-15

    We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [{sup 11}C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM). MET-PET and contrast-enhanced MRI with Gd-DTPA were performed in 12 uniformly pretreated patients with recurrent GBM. To calculate the volumes in cubic centimetres, a threshold-based volume-of-interest (VOI) analysis of the metabolically active tumour volume (MET uptake indexes of {>=}1.3 and {>=}1.5) and of the area of Gd-DTPA enhancement was performed after coregistration of all images. In all patients, the metabolically active tumour volume as shown using a MET uptake index of {>=}1.3 was larger than the volume of Gd-DTPA enhancement (30.2 {+-} 22.4 vs. 13.7 {+-} 10.6 cm{sup 3}; p = 0.04). Metabolically active tumour volumes as shown using MET uptake indexes of {>=}1.3 and {>=}1.5 and the volumes of Gd-DTPA enhancement showed a positive correlation (r = 0.76, p = 0.003, for an index of {>=}1.3, and r = 0.74, p = 0.005, for an index of {>=}1.5). The present data suggest that in patients with recurrent GBM the metabolically active tumour volume may be substantially underestimated by Gd-DTPA enhancement. The findings support the notion that complementary information derived from MET uptake and Gd-DTPA enhancement may be helpful in developing individualized, patient-tailored therapy strategies in patients with recurrent GBM. (orig.)

  5. Synthesis and preclinical evaluation of carbon-11 labelled N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a PET tracer for NR2B subunit-containing NMDA receptors

    International Nuclear Information System (INIS)

    Introduction: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in learning and memory. Overactivation is thought to play an important role in neurodegenerative disorders such as Alzheimer's disease. Currently, it is not possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NR2B binding site of the NMDA receptor. Methods: N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was radiolabelled with carbon-11 in the phenyl moiety. Biodistribution and blocking studies were carried out in anaesthetized mice and in non-anaesthetized rats. Results: N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was prepared in 49 ± 3% (decay-corrected) yield, affording 4.1 ± 0.3 GBq of formulated product at the end of synthesis with a radiochemical purity of > 99% and with a specific activity of 78 ± 10 GBq/μmol. Conclusion: A new NR2B PET ligand was developed in high yield. [11C]4 readily enters the brain and binds to the NR2B subunit-containing NMDAr in the rodent brain. High sigma-1 receptor binding may, however, limit its future application as a PET probe for imaging the NR2B subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and therefore can complicate interpretation of preclinical in vivo results. In addition, effects of endogenous compounds cannot be excluded. Despite these potential limitations, further studies are warranted to investigate the values of [11C]4 as an NR2B PET ligand

  6. Tetra- and mono-organotin reagents in palladium-mediated cross-coupling reactions for the labeling with carbon-11 of PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, T.; Huiban, M.; Sobrio, F.; Perrio, C.; Barre, E. [Groupe de Dev Methodol en Tomographie par Emission de Positons, UMR CEA 2E, Universite deCaen, Centre Cyceron, F-14070 Caen Cedex (France); Fouquet, A.; Huet, A. [Laboratoire de Chimie Organique et Organometallique, UMR CNRS 3802, Univ Bordeaux I, F-33405 Talence Cedex (France)

    2008-07-01

    The palladium-catalyzed cross-coupling reactions between a (trimethylstannyl)arene and [{sup 11}C]methyl iodide (Stille reaction) or between an aryl halide and a [{sup 11}C]monomethyltin reagent issued from Lappert's stannylene, were developed for the synthesis of polyfunctional [{sup 11}C]methyl quinolines and quinoline-imides as potential tracers for positron emission tomography (PET). (authors)

  7. Investigations of acetonitrile solvent cluster formation in supercritical carbon dioxide, and its impact on microscale syntheses of carbon-11-labeled radiotracers for PET

    International Nuclear Information System (INIS)

    A new strategy has been developed for synthesizing positron emission tomography (PET) radiotracers using [11C]methyl iodide. This strategy relies on the ability of organic co-solvents to cluster within mixtures of supercritical fluids resulting in localized regions of high density which can serve as microscopic pockets for reaction. We've shown that acetonitrile will cluster about dilute solutes when mixtures of this co-solvent with carbon dioxide are forced to behave as a homogeneous fluid at the critical point. We applied this strategy in a systematic investigation of the conditions for optimized reaction between methyl iodide and L-α-methyl-N-2-propynyl phenethylamine (nordeprenyl) to yield L-deprenyl. Variables such as temperature, ultraviolet light exposure, co-solvent concentration, system pressure, and methyl iodide concentration were explored. The synthesis of radioactive [11C]-L-deprenyl using no-carrier-added concentrations of [11C]methyl iodide was also tested. Results showed that greater than 90% radiochemical yield of the desired product could be attained using 40 times less labeling substrate than in conventional PET tracer syntheses

  8. Brain protein synthesis in normal and demented patients. A study by P.E.T. with 11C-L methionine

    International Nuclear Information System (INIS)

    A compartmental model representing protein synthesis in the brain was validated experimentally in 9 baboons. After sequential injections of 11C, 3H and 14C methionines on the same animal, followed by P.E.T. recording of the γ activity in a chosen brain section with time, the distribution of methionine injected into the different compartments of the model after a bolus was measured by crushing and precipitation with T.C.A. The agreement between direct in vitro findings and computed results is excellent. This method of studying brain protein synthesis in vivo was applied to 28 Alzheimer dementia cases and 20 normal subjects of the same age. The correlation between the results of clinical and psychometric tests and the brain protein synthesis activity confirms an anomaly in this biochemical synthesis process during the illness. A 65% fall in activity may be found in the frontal lobes of certain patients

  9. Carbon-11 labelling of eticlopride in two different positions - a selective high-affinity ligand for the study of dopamine D-2 receptors using PET

    International Nuclear Information System (INIS)

    A new highly selective high-affinity dopamine D-2 receptor antagonist, eticlopride ((-)-(S)-5-chloro-3-ethyl-N-(1-ethyl-2-pyrrolidinyl)methyl)-6-methoxysalicylamide), was labelled with 11C in two different positions ([N-ethyl-11C]eticlopride (I) and ([methyl-11C]eticlopride (II)). Product I was prepared by N-alkylation of the N-desethyl compound with [11C]ethyl iodide. II was prepared by O-alkylation of the diphenolic precursor with [11C]methyl iodide followed by separation of the two methylated products. The radiochemical yields were 15-20% (EOB) with an overall synthesis time of 45-60 min. Both compounds were isolated by semi-preparative HPLC and the radiochemical purity was in both cases > 99%. I was injected i.v. in a Cynomolgus monkey and brain radioactivity was measured by positron emission tomography (PET). The specific activity was 70 Ci/mmol at time of injection. There was a marked accumulation of radioactivity in the basal ganglia, regions known to have a high density of dopamine D-2 receptors. (author)

  10. A refined method for quantification of myocardial oxygen consumption rate using mean transit time with carbon-11-acetate and dynamic PET.

    Science.gov (United States)

    Choi, Y; Huang, S C; Hawkins, R A; Hoh, C K; Krivokapich, J; Buxton, D B; Armbrecht, J J; Sun, K T; Phelps, M E; Schelbert, H R

    1993-11-01

    The utility of the mean transit time equation was investigated for estimation of the myocardial clearance rate constant of 11C-acetate, which is proportional to myocardial oxygen consumption rates. The mean transit time approach was also employed to generate parametric images of the clearance rate constant of 11C-acetate with dynamic PET imaging in 20 normal human studies. Input function delays and cutoff errors due to the truncation of the myocardial tissue time-activity curve at a finite time were corrected. The clearance rate constants estimated by mean transit time correlated well with the estimates by conventional monoexponential fitting (15 min (truncation time): Y = 0.01 + 0.94X, correlated coefficient (r) = 0.99; 16 min: Y = 0.03 + 0.94X, r = 0.98; 20 min: Y = 0.03 + 0.84X, r = 0.99). The clearance rate constants estimated by the mean transit time approach also correlated well (r = 0.94) with the measured rate-pressure products. The quality and noise level of parametric images of the clearance rate constants generated by mean transit time are improved over those generated by monoexponential fitting. Additional advantages of the mean transit time approach compared to the standard monoexponential fitting method for estimating myocardial clearance rate constant of 11C-acetate include ease of input function delay correction, less sensitivity to the shape of the input function and elimination of subjective data selection of the linear portion of the clearance data on a semilog plot. Thus, this approach is expected to facilitate objective quantitative analysis of indices of myocardial oxygen consumption. PMID:8229256

  11. Synthesis and carbon-11-labeling of p-MeO-SSR180575, a novel indoleacetamide-based candidate for PET imaging of the peripheral benzodiazepine receptor (TSPO 18 kDa)

    International Nuclear Information System (INIS)

    Complete text of publication follows: Objectives: The 3-iso-quinolinecarboxamide [11C]PK11195, despite its low brain uptake and high level of nonspecific binding, is still the most widely used PET-radioligand for the in vivo imaging of the peripheral benzodiazepine receptor (PBR or TSPO 18 kDa). Several new PBR radioligands are currently developed to replace [11C]PK11195, e.g the pyrazolo[1, 5-a]pyrimidine-acetamides [11C]DPA-713 and [18F]DPA-714, the imidazo[1, 2-a]pyridine-acetamides [11C]CLINME and [18F]PBR111 and the N-benzyl-N-(2-phenoxy-aryl)- acetamides [11C]PBR28 and [18F]FEDAA1106. Another attractive newly identified chemical class of structures are the indole-acetamides and notably compounds derived from the lead compound SSR180575. Herein are reported the synthesis and the labelling with the positron-emitter carbon-11 (half-life: 20.38 min) of a novel derivative of SSR180575, bearing a para methoxy function on its phenyl ring. Methods: p-MeO-SSR180575 (1) was synthesized from commercially available 4-chloro-2-nitrotoluene in 10 steps. O-demethylation, performed with a boron tribromide solution in dichloromethane at low temperature, afforded the free phenol derivative 2. Carbon-11 labeling of p-MeO-SSR180575 (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprised (1) trapping of [11C]MeOTf at -10 C in acetone (0.3 mL) containing the nor-derivative 2 (O-demethylated, 0.6-0.9 mg) and aq. 3N NaOH (8 μL); (2) heating at 110 C for 2 min; (3) concentration to dryness and taking up the residue in 1.0 mL of the HPLC mobile phase; (4) purification using semi-preparative reversed-phase HPLC (Waters Symmetry C-18 - eluent: CH3CN / H2O / TFA: 50 / 50 / 0.1 (v:v:v) - flow rate: 5 mL/min - detection at 254 nm) and (5) SepPakR Plus C-18-based formulation for i.v. injection. Results: p-MeO-SSR180575 (1) was obtained in 10% overall yield. The tricky and low-yielding step in our approach was the pyridazine ring formation reaction that proceeded

  12. Accuracy of methionine-PET in predicting the efficacy of heavy-particle therapy on primary adenoid cystic carcinomas of the head and neck

    International Nuclear Information System (INIS)

    We evaluated whether or not PET or PET/CT using L-methyl-[11C]-methionine (MET) can allow for the early prediction of local recurrence and metastasis, as well as the prognosis (disease-specific survival), in patients with adenoid cystic carcinoma of the head and neck treated by carbon ion beam radiotherapy. This was a retrospective cohort study of sixty-seven patients who underwent a MET-PET or PET/CT study prior to and one month after the completion of carbon ion radiotherapy (CIRT). The minimum follow-up period for survivors was 12 months. The MET accumulation of the tumor was evaluated using the semiquantitative tumor to normal tissue ratio (TNR). A univariate analysis was conducted using the log-rank method, and the Cox model was used in a multivariate survival regression analysis. The average TNR prior to and following treatment was 4.8 (±1.5) and 3.0 (±1.3), respectively, showing a significant decrease following treatment. In the univariate analysis, a high TNR prior to treatment (TNRpre) was a significant factor for predicting the occurrence of metastasis and the disease-specific survival. A high TNR following treatment (TNRpost) was a significant factor for predicting the development of local recurrence. The residual ratio of TNR changes (TNRratio) seemed to be less useful than the TNRpre. In the multivariate analysis, the TNRpost and tumor size were the factors found to significantly influence the risk of local recurrence. The TNRpre, TNRratio and tumor size were all significant factors influencing the occurrence of metastasis. Regarding the disease-specific survival, the TNRpre and age were the only factors with a significant influence on the outcome. The TNRpre was a factor that was significantly related to the occurrence of metastasis and the disease-specific survival after CIRT for adenoid cystic carcinoma of the head and neck. The TNRpost was a factor that was significantly related to the development of local recurrence. Thus, MET-PET or PET/CT can

  13. Direct comparison of {sup 18}F-FDG and {sup 11}C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value

    Energy Technology Data Exchange (ETDEWEB)

    Laere, Koen Van; Ceyssens, Sarah; Mortelmans, Luc [University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); Calenbergh, Frank Van [University Hospital Leuven, Department of Neurosurgery, Leuven (Belgium); Groot, Tjibbe de; Bormans, Guy [University Hospital Leuven, Laboratory of Radiopharmaceutical Chemistry, Leuven (Belgium); Menten, Johan [University Hospital Leuven, Division of Radiotherapy, Leuven (Belgium); Flamen, Patrick [University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); Bordet Hospital, Division of Nuclear Medicine, Brussels (Belgium)

    2005-01-01

    {sup 18}F-fluorodeoxyglucose (FDG) and {sup 11}C-methionine (MET) PET imaging studies allow the investigation of metabolism and amino acid transport in brain tumours. Their (relative) usefulness and prognostic value in suspected recurrence or progression of primary brain tumours after previous therapy is an issue of debate. The aim of this study was to compare directly both radioligands in this setting. Cerebral uptake of FDG and MET was determined sequentially on the same day in 30 patients (21 males, nine females; age 40.4{+-}15.6 years), on average 4.0 years (range 0.1-18) after therapy for a primary brain tumour (23 grade II-IV astrocytomas, four oligodendrogliomas and three mixed oligo-astrocytomas). Images were acquired on a Siemens HR+ dedicated PET camera. Two observers scored FDG and MET scans independently. Semi-quantitative indices defined by the tumour (maximum)-to-background ratio were calculated based on manual ROI delineation and by using MET ROIs for FDG after automated co-registration. Patient follow-up was conducted until the last contact with inconspicuous clinical findings (average 41 months, range 12-62 months after PET) [(n=10)] or until death (n=20). Overall median survival was 15.0 months. MET showed pathologically increased uptake in 28/30 scans, and FDG in 17/30. The inter-observer agreement was 100% for MET and 73% for FDG. Using Kaplan-Meier survival analysis, significant differences were found for both FDG (cut-off 0.8, log-rank p=0.007) and MET (cut-off 2.2, log-rank p=0.014). The combination of FDG and MET information resulted in the highest prognostic accuracy (p=0.003), while MET alone was the best prognostic predictor in the subgroup of patients with primary astrocytoma (n=23). FDG and MET PET studies provide complementary prognostic information in patients with suspected brain tumour recurrence or progression after primary therapy. MET is considered the single agent of choice in the evaluation of these patients because of its

  14. Ethanolic Carbon-11 Chemistry: the Introduction of Green Radiochemistry

    OpenAIRE

    Shao, Xia; Fawaz, Maria V.; Jang, Keunsam; Scott, Peter J. H.

    2014-01-01

    The principles of green chemistry have been applied to a radiochemistry setting. Eleven carbon-11 labeled radiopharmaceuticals have been prepared using ethanol as the only organic solvent throughout the entire manufacturing process. The removal of all other organic solvents from the process simplifies production and quality control (QC) testing, moving our PET Center towards the first example of a green radiochemistry laboratory. All radiopharmaceutical doses prepared are suitable for clinica...

  15. Differentiation of Brain Tumor Recurrence from Post-Radiotherapy Necrosis with 11C-Methionine PET: Visual Assessment versus Quantitative Assessment.

    Directory of Open Access Journals (Sweden)

    Ryogo Minamimoto

    Full Text Available The aim of this multi-center study was to assess the diagnostic capability of visual assessment in L-methyl-11C-methionine positron emission tomography (MET-PET for differentiating a recurrent brain tumor from radiation-induced necrosis after radiotherapy, and to compare it to the accuracy of quantitative analysis.A total of 73 brain lesions (glioma: 31, brain metastasis: 42 in 70 patients who underwent MET-PET were included in this study. Visual analysis was performed by comparison of MET uptake in the brain lesion with MET uptake in one of four regions (around the lesion, contralateral frontal lobe, contralateral area, and contralateral cerebellar cortex. The concordance rate and logistic regression analysis were used to evaluate the diagnostic ability of visual assessment. Receiver-operating characteristic curve analysis was used to compare visual assessment with quantitative assessment based on the lesion-to-normal (L/N ratio of MET uptake.Interobserver and intraobserver κ-values were highest at 0.657 and 0.714, respectively, when assessing MET uptake in the lesion compared to that in the contralateral cerebellar cortex. Logistic regression analysis showed that assessing MET uptake in the contralateral cerebellar cortex with brain metastasis was significantly related to the final result. The highest area under the receiver-operating characteristic curve (AUC with visual assessment for brain metastasis was 0.85, showing no statistically significant difference with L/Nmax of the contralateral brain (AUC = 0.89 or with L/Nmean of the contralateral cerebellar cortex (AUC = 0.89, which were the areas that were the highest in the quantitative assessment. For evaluation of gliomas, no specific candidate was confirmed among the four areas used in visual assessment, and no significant difference was seen between visual assessment and quantitative assessment.The visual assessment showed no significant difference from quantitative assessment of MET-PET

  16. Detection and Characterization of Parathyroid Adenoma/Hyperplasia for Preoperative Localization: Comparison Between {sup 11}C-Methionine PET/CT and {sup 99m}Tc-Sestamibi Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, In Kook; Cheon, Gi Jeong; Paeng, Jin Chul; Kang, Keon Wook; Chung, Junekey; Lee, Dong Soo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    {sup 11}C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for detection of parathyroid adenoma; however, the reported detection rate has been variable. The current study was intended to investigate detection sensitivity and preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia (PH) on Met-PET/CT compared with {sup 99m}Tc-sestamibi (MIBI) scintigraphy in patients with primary hyperparathyroidism (HPT) or suspected PA. Met-PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine physicians unaware of pathologic results. Detection sensitivities and preoperative localization of detected parathyroid tissues into five predefined segments were evaluated by visual assessment and semiquantitative analysis with ratio of standardized uptake values (SUVR) between parathyroid tissue and normal lung as reference. Linear regression analysis with SUVR and serum parathyroid hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained for a calculated SUVR by using linear regression model from the result of previous linear regression analysis between SUVR and sPTH. In 16 patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 % (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically confirmed PA and PH cases only, respectively. Met-PET/CT showed higher performance than MIBI scintigraphy in localization of parathyroid tissues; correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with sPTH by linear regression analysis (sPTH=39.53ΧSUVR-89.84, p=0.0383). There was a borderline significant difference in pPTH between PH and PA (35.1 vs 204.7±164.0, p=0.052),while there was no significant difference in sPTH between PH

  17. PET STUDIES WITH L-[1-C-11]TYROSINE, L-[METHYL-C-11]METHIONINE AND F-18 FLUORODEOXYGLUCOSE IN PROLACTINOMAS IN RELATION TO BROMOCRYPTINE TREATMENT

    NARCIS (Netherlands)

    DAEMEN, BJG; ZWERTBROEK, R; ELSINGA, PH; PAANS, AMJ; DOORENBOS, H; VAALBURG, W

    1991-01-01

    Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-[1-C-11]tyrosine, L-[methyl-C-11]methionine and F-18-fluorodeoxyglucose (18FDG). Using L-[1-C-11]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocryptine. At 18

  18. A quartz-lined carbon-11 target: striving for increased yield and specific activity

    DEFF Research Database (Denmark)

    Koziorowski, Jacek; Larsen, Peter; Gillings, Nic

    2010-01-01

    The increased demand for high specific radioactivity neuroreceptor ligands for positron emission tomography (PET) requires the production of high specific radioactivity carbon-11 in high yields. We have attempted to address this issue with the development of a new quartz-lined aluminium target fo...

  19. PET

    DEFF Research Database (Denmark)

    Mariager, Rasmus Mølgaard; Schmidt, Regin; Heiberg, Morten Rievers

    PET handler om den hemmelige tjenestes arbejde under den kolde krig 1945-1989. Her fortæller Regin Schmidt, Rasmus Mariager og Morten Heiberg om de mest dramatiske og interessante sager fra PET's arkiv. PET er på flere måder en udemokratisk institution, der er sat til at vogte over demokratiet....... Dens virksomhed er skjult for offentligheden, den overvåger borgernes aktiviteter, og den registrerer følsomme personoplysninger. Historien om PET rejser spørgsmålet om, hvad man skal gøre, når befolkningen i et demokrati er kritisk indstillet over for overvågningen af lovlige politiske aktiviteter......, mens myndighederne mener, at det er nødvendigt for at beskytte demokratiet. PET er på en gang en fortælling om konkrete aktioner og begivenheder i PET's arbejde og et stykke Danmarkshistorie. Det handler om overvågning, spioner, politisk ekstremisme og international terrorisme.  ...

  20. Ethanolic carbon-11 chemistry: The introduction of green radiochemistry

    International Nuclear Information System (INIS)

    The principles of green chemistry have been applied to a radiochemistry setting. Eleven carbon-11 labeled radiopharmaceuticals have been prepared using ethanol as the only organic solvent throughout the entire manufacturing process. The removal of all other organic solvents from the process simplifies production and quality control (QC) testing, moving our PET Center towards the first example of a green radiochemistry laboratory. All radiopharmaceutical doses prepared are suitable for clinical use. - Highlights: • We report application of the principles of green chemistry to a radiochemistry setting. • Radiopharmaceuticals are prepared using ethanol as the only organic solvent. • Green radiochemistry simplifies production and QC in busy clinical production laboratories. • Residual solvent analysis can be relegated to a quarterly or annual QC test

  1. Radiochirurgie und stereotaktisch fraktionierte Strahlentherapie am Linearbeschleuniger bei Patienten mit Meningeomen;Wertigkeit der L-[Methyl-11C] Methionin (MET)-PET-Untersuchung als Ergänzung zu morphologischen bildgebenden Verfahren wie CT und MRT bei der Erstellung der Therapieplanung und Definition des Zielvolumens der Schädelbasismeningeome

    OpenAIRE

    Ciuchendea-Dobrei, Mihaela-Andreea

    2012-01-01

    Diese Studie untersuchte die Effektivität der stereotaktischen Strahlentherapie von gutartigen Schädelbasismeningeomen sowie die Wertigkeit der Methionin-PET-Bildgebung für die Bestrahlungsplanung. Bei 137 Patienten zeigte sich nach fraktionierter stereotaktischer Strahlentherapie (121 Patienten) bzw. Radiochirurgie (16 Patienten) eine Ansprechrate von 26,3% und eine Tumorkontrollrate von 93% nach einer medianen Nachbeobachtungszeit von 32 Monaten. Die Symptome verbesserten sich in 38% de...

  2. Evaluation of clinial usefulness of [sup 11]C-methionine positron emission tomography ([sup 11]C-MET-PET) as a tool for liver functional imaging

    Energy Technology Data Exchange (ETDEWEB)

    Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi (Chiba Univ. (Japan). School of Medicine) (and others)

    1994-03-01

    We studied [sup 11]C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of [sup 11]C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of [sup 3]H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of [sup 11]C-MET, the increase in rate of radioactivity of [sup 11]C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since [sup 11]C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author).

  3. Experience with carbon-11 choline positron emission tomography in prostate carcinoma

    International Nuclear Information System (INIS)

    We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node 11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration. (orig.)

  4. Studies to label Alfentanil with carbon-11

    Energy Technology Data Exchange (ETDEWEB)

    Feliu, A.L. (Forschungzentrum Juelich GmbH (Germany). Inst. fuer Chemie I)

    1992-09-01

    Methodology applicable to the synthesis of no-carrier-added (O-methyl-{sup 11}C)alfentanil was developed. The sequence consisted of ({sup 11}C)methylation and propionylation of N-aryl-4-(hydroxymethyl)-4-(N-anilino)-piperidines 1a and 1c, followed by the chemoselective hydrolysis of bulk byproducts to facilitate isolation of the NCA carbon-11-labeled product by prep-HPLC. All three steps could be performed without isolation of intermediates in a single reaction vessel. (author).

  5. Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia

    DEFF Research Database (Denmark)

    Kofoed, K F; Hansen, P R; Holm, S;

    2011-01-01

    Preserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute...

  6. Some examples of the use of carbon 11-labelled molecules in medical research

    International Nuclear Information System (INIS)

    If a radioelement is to be useful for medical diagnosis it must: be an indicator of a normal or pathological biological process; have a half-life consistent with the duration of the biological phenomenon to be observed; emit a suitable radiation. Carbon 11 is one of the radionuclides which best satisfies these different requirements. It is shown how this radioelement, of 20-minute half-life, may be incorporated into psychotropic drugs and biologically useful molecules with enough speed to have an available radioactivity adequate for diagnostic examinations. Two examples are described, one concerning the metabolism of a neuroleptic, chlorpromazine-11C, the other the passage of methionine-11C through the blood brain barrier during a congenital disease, phenylketonuria

  7. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  8. Imaging for carbon translocation to a fruit of tomato with carbon-11-labeled carbon dioxide and positron emission tomography

    International Nuclear Information System (INIS)

    Carbon kinetics in the fruit is an agricultural issue on the growth and development of the fruit to be harvested. Particularly, photo-assimilate translocation and distribution are important topics for understanding the mechanism. In the present work, carbon-11 (11C) labeled photo-assimilate translocation into fruits of tomato has been imaged using carbon-11-labeled carbon dioxide and the positron emission tomography (PET). Dynamic PET data of gradual increasing of 11C activity and its distribution is acquired quantitatively in intact plant body. This indicates that the three dimensional photo-assimilate translocation into the fruits is imaged successfully and carbon kinetics is analyzed to understand the plant physiology and nutrition. (authors)

  9. Impact of [11C]Methionine Positron Emission Tomography for Target Definition of Glioblastoma Multiforme in Radiation Therapy Planning

    International Nuclear Information System (INIS)

    Purpose: The purpose of this work was to define the optimal margins for gadolinium-enhanced T1-weighted magnetic resonance imaging (Gd-MRI) and T2-weighted MRI (T2-MRI) for delineating target volumes in planning radiation therapy for postoperative patients with newly diagnosed glioblastoma multiforme (GBM) by comparison to carbon-11-labeled methionine positron emission tomography ([11C]MET-PET) findings. Methods and Materials: Computed tomography (CT), MRI, and [11C]MET-PET were separately performed for radiation therapy planning for 32 patients newly diagnosed with GBM within 2 weeks after undergoing surgery. The extent of Gd-MRI (Gd-enhanced clinical target volume [CTV-Gd]) uptake and that of T2-MRI of the CTV (CTV-T2) were compared with the extent of [11C]MET-PET (CTV--[11C]MET-PET) uptake by using CT--MRI or CT--[11C]MET-PET fusion imaging. We defined CTV-Gd (x mm) and CTV-T2 (x mm) as the x-mm margins (where x = 0, 2, 5, 10, and 20 mm) outside the CTV-Gd and the CTV-T2, respectively. We evaluated the relationship between CTV-Gd (x mm) and CTV-- [11C]MET-PET and the relationship between CTV-T2 (x mm) and CTV-- [11C]MET-PET. Results: The sensitivity of CTV-Gd (20 mm) (86.4%) was significantly higher than that of the other CTV-Gd. The sensitivity of CTV-T2 (20 mm) (96.4%) was significantly higher than that of the other CTV-T2 (x = 0, 2, 5, 10 mm). The highest sensitivity and lowest specificity was found with CTV-T2 (x = 20 mm). Conclusions: It is necessary to use a margin of at least 2 cm for CTV-T2 for the initial target planning of radiation therapy. However, there is a limit to this setting in defining the optimal margin for Gd-MRI and T2-MRI for the precise delineation of target volumes in radiation therapy planning for postoperative patients with GBM.

  10. Synthesis of carbon-11 labeled dexetimide and levetimide for studying muscarinic acetylcholine receptors

    International Nuclear Information System (INIS)

    The localization and quantitation of the muscarinic acetylcholine receptor (m-AChR) in the living human brain using a non-invasive method, such as positron emission tomography (PET), may provide valuable information about receptor changes which have been observed post mortem in patients with Huntington's chorea and Alzheimer's dementia, as well as normal brain mechanisms mediated by the m-AChR. Although quinuclidinyl benzilate has been radioiodinated and radiomethylatd, the former is not useful with PET and the latter does not penetrate the blood-brain barrier; therefore, the authors chose to radiolabel dexetimide, a ligand which labels m-AChR in vitro and in vivo, and levetimide, its inactive enantiomer. Carbon-11 labeled carbon dioxide is bubbled through a tetrahydrofuran (THF) solution of phenylmagnesium chloride (1 M, l ml) after which 2 mg of lithium aluminium hydride is added in THF (500 μl). After evaporation of the solvent, 48% hydriodic acid (l ml) is added and the solution is heated for 1 minute. Carbon-11 labeled benzyl iodide is extracted into methylene chloride, added to a solution of nor-benzyl dexetimide or levetimide, and heated for several minutes. Purification is accomplished using semi-preparative reverse phase high performance liquid chromatography (HPLC). Analytical HPLC is used to determine the radiochemical purity and specific activity

  11. 18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    György Trencsényi

    2014-01-01

    Full Text Available Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1 in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb and cyclosporine A (CSA is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG, 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT, and [18F]fluoroazomycin-arabinofuranoside (18FAZA for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+ and negative (Pgp− human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.

  12. PET studies with L-(1- sup 11 C)tyrosine, L-(methyl- sup 11 C)methionine and sup 18 F-fluorodeoxyglucose in relation to bromocryptine treatment

    Energy Technology Data Exchange (ETDEWEB)

    Daemen, B.J.G.; Elsinga, P.H.; Paans, A.M.J.; Vaalburg, W. (Rijksuniversiteit Groningen (Netherlands). Dept. of Nuclear Medicine); Zwertbroek, R.; Doorenbos, H. (Rijksuniversiteit Groningen (Netherlands). Dept. of Endocrinology)

    1991-07-01

    Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-(1-{sup 11}C)tyrosine, L-(methyl-{sup 11}C)methionine and fluorodeoxyl glucose 18. Using L-(1-{sup 11}C)tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocryptine. At 18 h after bromocryptine intervention L-(1-{sup 11}C)tyrosine uptake into tumour was reduced with 28% (P<0.07). A correlation analysis of the bromocryptine-induced decrease in L-(1-{sup 11}C)tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocryptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with {sup 18}FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with L-(methyl-{sup 11}C)methionine. The tumour-imaging potential of L-(methyl-{sup 11}C)methionine and L-(1-{sup 11}C)tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for L-(1-{sup 11}C)tyrosine as compared to L-(methyl-{sup 11}C)methionine. L-(1-{sup 11}C)tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas. (orig.).

  13. Medical application of PET technology

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Choi, C. W.; An, S. H.; Woo, K. S.; Chung, W. S.; Yang, S. D.; Jun, G. S. and others

    1999-04-01

    We performed following studies using PET technology: 1. Clinical usefulness of [{sup 18}F]FDG whole body PET in malignant disease 2. Clinical usefulness of quantitative evaluation of F-18-FDG 3. Pilot study of C-11 methionine PET in brain tumor 4. PET study in patients with Parkinson's disease 5. A study on the clinical myocardial PET image. PET gives various metabolic information for the living human body, and is very important, new diagnostic modality. The PET study will give us the information of cancer patients such as early detection of cancer, staging, recurrence detection and characterization of cancer. The quantitative analysis using PET could be applied to evaluate the pathophysiology of various diseases and develop new drugs and develop new radiopharmaceuticals.

  14. Medical application of PET technology

    International Nuclear Information System (INIS)

    We performed following studies using PET technology: 1. Clinical usefulness of [18F]FDG whole body PET in malignant disease 2. Clinical usefulness of quantitative evaluation of F-18-FDG 3. Pilot study of C-11 methionine PET in brain tumor 4. PET study in patients with Parkinson's disease 5. A study on the clinical myocardial PET image. PET gives various metabolic information for the living human body, and is very important, new diagnostic modality. The PET study will give us the information of cancer patients such as early detection of cancer, staging, recurrence detection and characterization of cancer. The quantitative analysis using PET could be applied to evaluate the pathophysiology of various diseases and develop new drugs and develop new radiopharmaceuticals

  15. Carbon-11-labelling of a novel, trishomocubane-derived, high affinity and selectivity DAT ligand

    International Nuclear Information System (INIS)

    Complete text of publication follows: Objectives: Parkinson's disease, schizophrenia, attention deficit disorder and drug abuse are related to abnormalities within the brain's dopaminergic system. The neuronal dopamine transporter (DAT) plays a key role in regulating the synaptic concentration of dopamine and thus dopamine neurotransmission in the brain. Since the DAT can be considered as a marker of the integrity and number of the presynaptic striatal dopamine-producing neurons, considerable efforts have been spent in recent years on the design and development of DAT-selective radioligands for use in Positron Emission Tomography (PET) studies. Notably, the tropane PE2I and its fluorinated analogue LBT-999 were identified as having high affinity and selectivity for the DAT over the norepinephrine transporter (NET) and the serotonin transporter (SERT). Besides tropanes, only a few bicyclic frameworks, e.g. bicyclo[2.2.2]octanes, have delivered compounds with high affinity for the DAT. Recently, novel poly-carbocyclic DAT ligands with selectivity over the NET and the SERT were reported. The lead compound of this series (1, N-methyl-N-(3-fluoro) benzyl-pentacyclo[5.4.0.02,6.03,10.05,9] undec-8-ylamine, Ki = 1.2 nM, ≥ 8300-fold selectivity over NET and SERT) was selected as a potential candidate for imaging the DAT with PET and isotopically labelled with carbon-11 using [11C]methyl triflate. Methods: The trishomocubane derivatives 1 (reference) and 2 (precursor for labelling with carbon-11) were prepared from commercially available Cookson's diketone in 6 and 7 steps, respectively. Carbon-11 labelling of 1 was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprises (1) trapping at -10 C of [11C]MeOTf in acetone (0.4 mL) containing the nor-derivative 2 (0.6-0.9 mg, free base) and aq. 3N NaOH (8 μL); (2) heating at 110 C for 2 min; (3) concentration to dryness and taking up the residue in 1.0 mL of the HPLC mobile phase; (4) purification using semi

  16. Chiral dimethylamine flutamide derivatives-modeling, synthesis, androgen receptor affinities and carbon-11 labeling

    International Nuclear Information System (INIS)

    Most prostate cancers are androgen dependent upon initial diagnosis. On the other hand, some very aggressive forms of prostate cancer were shown to have lost the expression of the androgen receptor (AR). Although the AR is routinely targeted in endocrine treatment, the clinical outcome remains suboptimal. Therefore, it is crucial to demonstrate the presence and activity of the AR in each case of prostate cancer, before and after treatment. While noninvasive positron emission tomography (PET) has the potential to determine AR expression of tumor cells in vivo, fully optimized PET imaging agents are not yet available. Based on molecular modeling, three novel derivatives of hydroxyflutamide (Compounds 1-3) were designed and synthesized. They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo. Compounds 1-3 have AR binding that is similar or higher than that of the currently used commercial drugs. An automated carbon-11 radiolabeling route was developed, and the compounds were successfully labeled with a 10-15% decay-corrected radiochemical yield, 99% radiochemical purity and a specific activity of 4Ci/μmol end of bombardment (n=15). These labeled biomarkers may facilitate the future quantitative molecular imaging of AR-positive prostate cancer using PET and may also allow for image-guided treatment of prostate cancer

  17. Synthesis of carbon-11 labelled calcium channel antagonists

    International Nuclear Information System (INIS)

    A useful synthetic approach to carbon-11 labelled 1,4-dihydropyridines is described. Carbon-11 labelled calcium channel antagonists 11C-Nifedipine, 11C-Nisoldipine, 11C-nitrendipine and 11C-CF3-Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with 11CH3I produced the labelled compounds in very good chemical and radiochemical yields (94%). (author)

  18. Labeled plasma metabolites of L-methyl-hydrogen-3-methionine and L-methyl-carbon-14-methionine in the dog

    International Nuclear Information System (INIS)

    The validity of the mathematical models that attempt to describe positron emission tomography (PET) images produced with [11CH3] methionine in terms of rates of local cerebral protein synthesis has yet to be established. A major objection to current models is that the use of methionine labeled at the methyl position results in the dispersal of the label among various methyl-accepting compounds that appear in the plasma and may then enter the brain. One approach to overcoming this problem has been the use of ''standard'' corrections for the activity contributed to plasma by labeled plasma protein and labeled serine. In order to determine the validity of this approach, the metabolic fate of labeled methionine was studied in six dogs. After injection with either [C3H3] methionine or [14CH3] methionine arterial blood was sampled. Plasma fractions containing protein were separated by fast gel filtration, counted with standard scintillation techniques, and their radioactivity was compared with total plasma radioactivity. Plasma was also separated by high-pressure liquid chromatography into methionine, serine, and nonmethionine or serine-containing fractions. These fractions were counted, and their radioactivity was compared with total plasma radioactivity. Labeled protein appeared in plasma about 20 minutes postinjection and then increased steadily. Labeled serine also appeared and reached a peak value of 9.4 +/- 2.1% of plasma activity at 40 minutes. Of greatest interest was the appearance in later plasma samples of increasing amounts of activity contained in nonserine low molecular weight metabolites of methionine. At 40 minutes, those metabolites made up 27 +/- 6.9% of total plasma activity

  19. Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with positron emission tomography

    International Nuclear Information System (INIS)

    Exploration of the living human brain in real-time and in a noninvasive way was for centuries only a dream, made, however, possible today with the remarkable development during the four last decades of powerful molecular imaging techniques, and especially positron emission tomography (PET). Molecular PET imaging relies, from a chemical point of view, on the use and preparation of a positron-emitting radiolabelled probe or radiotracer, notably compounds incorporating one of two short-lived radionuclides fluorine-18 (T1/2: 109.8 min) and carbon-11 (T1/2: 20.38 min). The growing availability and interest for the radio-halogen fluorine-18 in radiopharmaceutical chemistry undoubtedly results from its convenient half-life and the successful use in clinical oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). The special interest of carbon-11 is not only that carbon is present in virtually all biomolecules and drugs allowing therefore for isotopic labelling of their chemical structures but also that a given molecule could be radiolabelled at different functions or sites, permitting to explore (or to take advantage of) in vivo metabolic pathways. PET chemistry includes production of these short-lived radioactive isotopes via nuclear transmutation reactions using a cyclotron, and is directed towards the development of rapid synthetic methods, at the trace level, for the introduction of these nuclides into a molecule, as well as the use of fast purification, analysis and formulation techniques. PET chemistry is the driving force in molecular PET imaging, and this special issue of the Journal of Labelled Compounds and Radiopharmaceuticals, which is strongly chemistry and radiochemistry-oriented, aims at illustrating, be it in part only, the state-of-the-art arsenal of reactions currently available and its potential for the research and development of specific molecular probes labelled with the positron emitters carbon-11 and fluorine-18,with optimal imaging properties for

  20. Methionine catabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    Perpète, Philippe; Duthoit, Olivier; De Maeyer, Simon; Imray, Louise; Lawton, Andrew I; Stavropoulos, Konstantinos E; Gitonga, Virginia W; Hewlins, Michael J E; Dickinson, J Richard

    2006-01-01

    The catabolism of methionine to methionol and methanethiol in Saccharomyces cerevisiae was studied using (13)C NMR spectroscopy, GC-MS, enzyme assays and a number of mutants. Methionine is first transaminated to alpha-keto-gamma-(methylthio)butyrate. Methionol is formed by a decarboxylation reaction, which yields methional, followed by reduction. The decarboxylation is effected specifically by Ydr380wp. Methanethiol is formed from both methionine and alpha-keto-gamma-(methylthio)butyrate by a demethiolase activity. In all except one strain examined, demethiolase was induced by the presence of methionine in the growth medium. This pathway results in the production of alpha-ketobutyrate, a carbon skeleton, which can be re-utilized. Hence, methionine catabolism is more complex and economical than the other amino acid catabolic pathways in yeast, which use the Ehrlich pathway and result solely in the formation of a fusel alcohol. PMID:16423070

  1. Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure

    International Nuclear Information System (INIS)

    Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35%±8%) who had undergone carbon-11 hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55±19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of 11C-HED retention (mean 0.184±0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with 11C-HED retention below the median and three in the group with 11C-HED retention above the median (P2), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11C-HED PET provides independent prognostic information in patients with CHF. (orig.)

  2. Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Pietilae, M.; Ukkonen, H. [Dept. of Medicine, Turku University Central Hospital (Finland); Turku PET Centre, Turku (Finland); Malminiemi, K. [Dept. of Clinical Chemistry, Tampere University Hospital (Finland); Saraste, M. [Dept. of Clinical Physiology, Turku University Central Hospital (Finland); Naagren, K.; Lehikoinen, P. [Turku PET Centre, Turku (Finland); Voipio-Pulkki, L.-M. [Dept. of Medicine, Turku University Central Hospital (Finland); Dept. of Medicine, Helsinki University Central Hospital (Finland)

    2001-03-01

    Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35%{+-}8%) who had undergone carbon-11 hydroxyephedrine ({sup 11}C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55{+-}19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of {sup 11}C-HED retention (mean 0.184{+-}0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with {sup 11}C-HED retention below the median and three in the group with {sup 11}C-HED retention above the median (P<0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO{sub 2}), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that {sup 11}C-HED PET provides independent prognostic information in patients with CHF. (orig.)

  3. Functional diagnosis of cancer using PET

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) can demonstrate increased metabolic demand as visual images, and it provides alternative information for diagnosis that can be used to complement morphological observations. This year, we carried out a study on the usefulness of methionine PET for diagnosis in ovarian cancer. In this study, 13 cases with ovarian tumor, 9 cases were original or recurrent malignant tumors and 4 cases were benign tumors, were studied by both C-11 methionine and FDG PET. All cases received the two PET studies at intervals of one week. C-11 methionine PET showed mean accumulation of 5.26±0.68 (tumor-to-muscle ratio (TMR)) in malignant group and 2.56±0.40 (TMR) in benign group which were significantly different by p-value=0.030. FDG PET showed mean accumulation of 5.80±1.24 standardized uptake value (SUV)) in malignant group and 2.44±0.40 (SUV) in benign group which were significantly different by p-value=0.029. We compared the diagnostic accuracy with C-11 methionine, FDG PET, X-ray CT and CA125 serum level. In C-11 methionine and FDG PET studies, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 88.9%, 75.0%, 88.9% and 75.0%, respectively. C-11 methionine and FDG-PET showed just the same diagnostic accuracy in our cases. In X-ray CT study, sensitivity, specificity, PPV and NPV were 55.6%, 75.0%, 83.3% and 42.9%, respectively. The tumor marker, CA125 level in the serum, showed that sensitivity, specificity, PPV and NPV were 55.6%, 25.0%, 62.5% and 20.0%, respectively. C-11 methionine PET was superior in diagnostic accuracy to usual diagnostic tools such as X-ray CT findings and CA125 serum level, and it had same diagnostic accuracy with FDG PET. C-11 methionine accumulated in normal liver and normal intestine physiologically, some cases showed that FDG was able to detect lesions in these organs better than C-11 methionine. But FDG accumulated in very high level in urinal system form kidney to bladder

  4. Local cerebral metabolic rate of 11C-L-Methionine in early stages of dementia, schizophrenia, Parkinson's disease

    International Nuclear Information System (INIS)

    A dynamic three-compartment model of methionine metabolism in brain was applied in human patients using 11C-L-Methionine and positron emission tomography (P.E.T). Psychometric evaluations of demented patients were correlated with a significant diminution of protein synthesis in the frontal area. This diminution was lower in ebephrenic patients (-17%) but was consistent with the results obtained with 18F glucose. No significant abnormality was detected in patients with Parkinson disease

  5. Synthesis and biological evaluation of carbon-11 and fluorine-18 labeled tracers for in vivo visualization of PDE10A

    International Nuclear Information System (INIS)

    Introduction: In vivo visualization of PDE10A using PET provides a tool to evaluate the role of PDE10A in various neuropsychiatric diseases and can also be useful in the clinical evaluation of PDE10A inhibitor drug candidates. We evaluated several carbon-11 and fluorine-18 labeled PDE10A inhibitors as potential PDE10A PET radioligands. Materials and Methods: [11C]MP10, [11C]JNJ42071965 and four other tracers were developed. Their biodistribution was evaluated in rats. Rat plasma and brain radiometabolites were quantified. Baseline microPET imaging was performed in normal rats and PDE10A knockout (KO) and wild-type (WT) mice. Blocking and displacement studies were conducted. The selectivity of the tracer binding was further studied in an ex vivo autoradiography experiment in PDE10A KO and WT mice. Results: Biodistribution showed brain uptake for all tracers in the striatum and wash-out from the cerebellum. [11C]1 (11C-MP10) had the highest specific uptake index (striatum (S) vs. cerebellum (C) ratios (S/C)-1) at 60 min (7.4). [11C]5 ([11C]JNJ42071965) had a high index at the early time points (1.0 and 3.7 at 2 and 30 min p.i., respectively). The affinity of [11C]4, [18 F]3 and [18 F]6 was too low to visualize PDE10A using microPET. [11C] 2 showed a specific binding, while kinetics of [11C]1 were too slow. [11C]5 reached equilibrium after 10 min (uptake index = 1.2). Blocking and displacement experiments in rats and baseline imaging in PDE10A KO mice showed specific and reversible binding of [11C]5 to PDE10A. Conclusions: We successfully radiolabeled and evaluated six radiotracers for their potential to visualize PDE10A in vivo. While [11C]1 had the highest striatal specific uptake index, its slow kinetics likely compromise clinical use of this tracer. [11C]5 has a relatively high striatum-to-background ratio and fast kinetic profile, which makes it a valuable carbon-11 alternative

  6. Methionine Uptake and Required Radiation Dose to Control Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-cc.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo [Division of Radiation Oncology, Tokyo Bay Advanced Imaging and Radiation Oncology Clinic, Makuhari, Chiba (Japan); Uchino, Yoshio [Division of Nuclear Medicine, Chiba Ryogo Center, Chiba (Japan); Itami, Makiko [Division of Surgical Pathology, Chiba Cancer Center, Chiba (Japan); Hasegawa, Yuzo; Kawasaki, Koichiro; Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2015-09-01

    Purpose: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. Methods and Materials: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. Results: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P=.005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P<.0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. Conclusions: Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

  7. Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec)

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Ding Yushin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Lin Kuoshyan [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Alexoff, David [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States)]. E-mail: fowler@bnl.gov

    2007-02-15

    Introduction: Imatinib mesylate (Gleevec) is a well known drug for treating chronic myeloid leukemia and gastrointestinal stromal tumors. Its active ingredient, imatinib ([4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridyl) -2-pyrimidinyl]amino]phenyl]benzamide), blocks the activity of several tyrosine kinases. Here we labeled imatinib with carbon-11 as a tool for determining the drug distribution and pharmacokinetics of imatinib, and we carried out positron emission tomography (PET) studies in baboons. Methods: [N-{sup 11}C-methyl]imatinib was synthesized from [{sup 11}C]methyl iodide and norimatinib was synthesized by the demethylation of imatinib (isolated from Gleevec tablets) according to a patent procedure [Collins JM, Klecker RW Jr, Anderson LW. Imaging of drug accumulation as a guide to antitumor therapy. US Patent 20030198594A1, 2003]. Norimatinib was also synthesized from the corresponding amine and acid. PET studies were carried out in three baboons to measure pharmacokinetics in the brain and peripheral organs and to determine the effect of a therapeutic dose of imatinib. Log D and plasma protein binding were also measured. Results: [N-{sup 11}C-methyl]imatinib uptake in the brain is negligible (consistent with P-glycoprotein-mediated efflux); it peaks and clears rapidly from the heart, lungs and spleen. Peak uptake and clearance occur more slowly in the liver and kidneys, followed by accumulation in the gallbladder and urinary bladder. Pretreatment with imatinib did not change uptake in the heart, lungs, kidneys and spleen, and increased uptake in the liver and gallbladder. Conclusions: [N-{sup 11}C-methyl]imatinib has potential for assessing the regional distribution and kinetics of imatinib in the human body to determine whether the drug targets tumors and to identify other organs to which the drug or its labeled metabolites distribute. Paired with tracers such as 2'deoxy-2'-[{sup 18}F]fluoro-D-glucose ({sup 18}FDG) and 3&apos

  8. Investigation on the role of integrated PET/MRI for target volume definition and radiotherapy planning in patients with high grade glioma

    International Nuclear Information System (INIS)

    Purpose: To evaluate the impact of fluid-attenuated-inversion-recovery MRI (FLAIR/MRI) and Carbon-11-labeled-methionine PET (11C-MET-PET) on high grade glioma (HGG) tumor volume delineation for radiotherapy planning. Material and methods: Sixty-nine patients with HGG were evaluated. The clinical target volumes (CTV1, generated by adding a 10 mm margin to FLAIRMRI area, CTV2 by adding a 20 mm margin to enhanced T1MRI) and biological target volume (BTV) were delineated on pre-operative MRI images and 11CMETPET respectively. Results: The overlap between CTV1 and CTV2 showed a low correlation between the two volumes with CTV1 not always fully included into the CTV2. In all cases the whole BTV was included into the CTV1, while in 35/69 patients (50%) part of BTV was outside the CTV2 despite larger margins were added. In all cases recurrences were within the CTV1 volume and in 19/38 (50%) partially outside the CTV2. In all patients relapse corresponded to the BTV area. Conclusions: Our data suggest that the target volume definition using FLAIR–MRI is more adequate compared to enhanced T1MRI. 11C-METPET uptake could help identify microscopic residual areas

  9. In vivo evaluation of carbon-11-labelled non-sarcosine-based glycine transporter 1 inhibitors in mice and conscious monkeys

    International Nuclear Information System (INIS)

    Introduction: Glycine transporter 1 (GlyT-1) is an attractive target in positron emission tomography (PET) studies. Here, we report the in vivo evaluation of three carbon-11-labelled non-sarcosine-type GlyT-1 inhibitors - [11C]SA1, [11C]SA2 and [11C]SA3 - as novel PET tracers for GlyT-1. Methods: The regional brain distributions of the three compounds in mice were studied at baseline and under receptor-blockade conditions with co-injection of carrier loading or pretreatment with an excess of selective GlyT-1 inhibitors (ALX-5407 and SSR504734). Metabolic stability was investigated by radio high-performance liquid chromatography. Dynamic PET scans in conscious monkeys were performed with/without selective GlyT-1 inhibitors. Results: The IC50 values of SA1, SA2 and SA3 were 9.0, 6400 and 39.7 nM, respectively. The regional brain uptakes of [11C]SA1 and [11C]SA3 in mice were heterogeneous and consistent with the known distribution of GlyT-1. [11C]SA2 showed low and homogeneous uptake in the brain. Most radioactivity in the brain was detected in unchanged form, although peripherally these compounds were degraded. Carrier loading decreased the uptake of [11C]SA1 in GlyT-1-rich regions. However, similar reductions were not observed with [11C]SA3. Pretreatment with ALX-5407 decreased the uptake of [11C]SA1 in GlyT-1-rich regions. In the monkey at baseline, regional brain uptake of [11C]SA1 was heterogeneous and consistent with the known GlyT-1 distribution. Pretreatment with selective GlyT-1 inhibitors significantly decreased the distribution volume ratio of [11C] SA1 in GlyT-1-rich regions. Conclusions: [11C]SA1 has the most suitable profile among the three carbon-11-labelled GlyT-1 inhibitors. Lead optimization of [11C]SA1 structure will be required to achieve in vivo selective GlyT-1 imaging.

  10. Carbon-11 labelled analogs of alanine by the Strecker synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Prenant, C.; Theobald, A.; Siegel, T.; Joachim, J.; Weber, K.; Haberkorn, U.; Oberdorfer, F. [Deutsches Krebsforschungszentrum, Heidelberg (Germany)

    1995-06-01

    Derivatives of alanine, {alpha}-[2-sup(11)C]aminoisobutyric acid 1a and {alpha}-(N-methyl)-[2-{sup 11} C]aminoisobutyric acid 1b were prepared for the in-vivo study of amino acid transport phenomena by positron-emission-tomography (PET). Compounds 1a and 1b were obtained by a Zelinski-Stadnikoff variant of the Strecker {alpha}-amino acid synthesis from in-situ formed [{sup 11} C]acetone in presence of sodium cyanide and either ammonium sulfate (for 1a) or methylamine hydrochloride (for 1b). The complete preparation required 50 min from the end of [{sup 11}C]CO{sub 2} production, and delivered 1.2 - 2 GBq of labelled product for application (2.4 -4%); not corrected for decay; related to trapped [{sup C}]CO{sub 2}. The specific activity of the labelled products was 16 to 20 GBq{center_dot}{mu}mol{sup -1}. The radiochemical and chemical purity of the preparations was greater than 98%. (Author).

  11. Groningen experience in production and application of fluorine-18 and carbon-11 labeled radiopharmaceuticals

    International Nuclear Information System (INIS)

    In this presentation the preparation of these tracers (fluorine-18 and carbon-11 labeled radiopharmaceuticals), as well as the present stage of development and evaluation, and the potential application in oncology will be discussed. (author)

  12. Methionine production--a critical review.

    Science.gov (United States)

    Willke, Thomas

    2014-12-01

    This paper presents an updated critical review about several attempts to contribute methionine (Met) to the world market with an emphasis on fermentation processes, especially from natural biological sources. Analytical methods for the determination of methionine are reviewed as well as applications in feed, food, pharmacy, and medicine. Fermentation studies published within the last five decades are elucidated critically, mainly with respect to the sulfur balance, substrate yield, and the analytical validity. From all the published fermentation data, it can be concluded that up to now no more than 5 g/L methionine are achievable without using genetically modified organisms (GMOs). The highest L-methionine concentration from natural sources reached so far amounts to 35 g/L and is published as a patent using a GMO of Escherichia coli. The review closes with a comprehensive overview of the role and activities of global methionine manufacturers. Some current market data is also presented. PMID:25381187

  13. Methionine metabolism in Yucatan miniature swine.

    Science.gov (United States)

    McBreairty, Laura E

    2016-06-01

    Methionine is an essential amino acid which when not incorporated into protein, can be converted to S-adenosylmethionine, the universal methyl donor in over 200 transmethylation reactions, which include creatine and phosphatidylcholine (PC) synthesis, as well as deoxyribonucleic acid (DNA) methylation. Following transmethylation, homocysteine is formed, which can be converted to cysteine via transsulfuration or remethylated to methionine by receiving a methyl group from folate or betaine. Changes to methyl group availability in utero can lead to permanent changes in epigenetic patterns of DNA methylation, which has been implicated in "fetal programming", a phenomenon associated with poor nutrition during fetal development that results in low birth weight and disease in later life. It has been shown that programming can also occur in the neonate. Our global objective was to understand how the variability of nutrients involved in methionine metabolism can affect methionine and methyl group availability. We hypothesize that nutrients that converge on methionine metabolism can affect methionine availability for its various functions. In this thesis, we used intrauterine growth restricted (IUGR) piglets to investigate whether a global nutritional insult in utero can lead to a perturbed methionine metabolism. Our results demonstrate that IUGR piglets have a lower capacity to dispose of homocysteine via both transsulfuration and remethylation pathways, as well as a lower incorporation of methyl groups into PC. The second objective of this thesis was to determine whether variation in methionine supply and demand can affect methionine availability. We demonstrated that stimulating either acute or chronic creatine synthesis leads to lower methyl incorporation into protein and PC in pigs. Furthermore, when methionine is limiting, supplementation with either folate or betaine leads to higher methionine availability for protein synthesis. Finally, because creatine is

  14. Imaging Spectrum and Pitfalls of 11C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions

    Science.gov (United States)

    Matsuda, Hiroshi; Kubota, Kazoo

    2016-01-01

    11C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of 11C-Met PET for general practitioners. Physiological 11C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during 11C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of 11C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of 11C-Met images could help prevent unfavorable clinical results caused by misdiagnoses. PMID:27134530

  15. Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma. A PET study

    NARCIS (Netherlands)

    Roelcke, U; Radu, EW; Hausmann, O; Vontobel, P; Maguire, RP; Leenders, KL

    1998-01-01

    We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), F-18-fluorodeoxyglucose (FDG), C-11-methionine (MET), and (82)Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volu

  16. Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo

    International Nuclear Information System (INIS)

    2-[1251]-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-[1231]-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-[1251]-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2 antagonist, inhibited binding. 2-[1231]-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-([11C]-Me)-2-Br-LSD (11C-MBL) from [11C]-methyl iodide and 2-Br-LSD for PET imaging trials. 11C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-[1251]-LSD. After 30 minutes, peak tissue to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited 11C-MBL binding. 11C-MBL is a promising candidate for PET studies of S2 receptors

  17. Propionyl-l-carnitine: Labelling in the N-methyl position with Carbon-11 and pharmacokinetic studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, Raymond J.; Law, Marilyn P.; Pike, Victor W.; Osman, Safiye; Poole, Keith G

    1995-08-01

    The prospective therapeutic, propionyl-l-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t{sub (1(2))} = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-l-carnitine hydrochloride with no-carrier-added [{sup 11}C]iodomethane (produced from cyclotron-produced [{sup 11}C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6,-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl-{sup 11}C]propionyl-l-carnitine in 62% radiochemical yield (decay-corrected from [{sup 11}C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl-{sup 11}C]Propionyl-l-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl-{sup 11}C]l-carnitine and [N-methyl-{sup 11}C]acetyl-l-carnitine.

  18. Propionyl-l-carnitine: Labelling in the N-methyl position with Carbon-11 and pharmacokinetic studies in rats

    International Nuclear Information System (INIS)

    The prospective therapeutic, propionyl-l-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t(1(2)) = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-l-carnitine hydrochloride with no-carrier-added [11C]iodomethane (produced from cyclotron-produced [11C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6,-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl-11C]propionyl-l-carnitine in 62% radiochemical yield (decay-corrected from [11C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl-11C]Propionyl-l-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl-11C]l-carnitine and [N-methyl-11C]acetyl-l-carnitine

  19. Methionine residues as endogenous antioxidants in proteins

    OpenAIRE

    Levine, Rodney L.; Mosoni, Laurent; Berlett, Barbara S.; Stadtman, Earl R.

    1996-01-01

    Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they can form disulfide bonds that contribute to protein structure. In contrast, the specific functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxi...

  20. Biosynthetic preparation of 35-S labelled methionine

    International Nuclear Information System (INIS)

    High specific activity methionine with sulfur-35 was prepared in our laboratory by growing Baker's yeast cells, in a medium containing 35S-sulfate. L-S35 methionine was prepared from the acid hydrolyzate of the proteins by chromatography on whatman paper. The specific activity was determined using o-phtaladehyde as a fluorophore to form a fluorescent complex. The specific activity was found to be usually greater than 800 Ci/mmol. (Author)

  1. Metabolism of 5-methylthioribose to methionine

    International Nuclear Information System (INIS)

    During ethylene biosynthesis, the H3CS-group of S-adenosylmethionine is released as 5'-methylthioadenosine, which is recycled to methionine via 5-methylthioribose (MTR). In mungbean hypocotyls and cell-free extracts of avocado, [14C]MTR was converted into labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB), as intermediates. Incubation of [ribose-U-14C]MTR with avocado extract resulted in the production of [14C]formate, indicating the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR. Tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract requires an amino donor. Among several potential donors examined, L-glutamine was the most efficient. Anaerobiosis inhibited only partially the oxidation of MTR to formate, KMB/HMB, and methionine by avocado extract. The role of O2 in the conversion of MTR to methionine is discussed

  2. Visualisation and assessment of the protein synthesis rate of lung cancer using carbon-11 tyrosine and positron emission tomography

    International Nuclear Information System (INIS)

    This study evaluated the potential role of L-(1-11C)-tyrosine positron emission tomography (TYR PET) for visualisation and quantification of protein metabolism in lung cancer. Dynamic TYR PET scans of the thorax were performed in 17 patients with lung cancer. Protein synthesis rate (PSR in μmol/min.l) and standardised uptake value (SUV, corrected for body measurements) of tumour tissue and contralateral normal tissue were calculated before and after chemotherapy or radiotherapy. All tumours [11 non-small cell lung carcinomas (NSCLCs), five small cell lung carcinomas (SCLCs), and one pleural mesothelioma] were visualised as a hot spot. The median PSR in tumour tissue was higher than that in corresponding contralateral normal lung tissue before [1.88 μmol/min.l (range 1.10-3.42) vs 0.40 μmol/min.l (range 0.12-0.86); P=0.003] and after treatment [1.33 μmol/min.l (range 0.45-2.21) vs 0.28 μmol/min.l (range 0.18-0.51); P<0.02]. In contrast to PSR of normal lung tissue, PSR of tumour tissue decreased significantly after therapy (P=0.03). Before therapy, no significant difference in PSR between NSCLCs and SCLCs was observed, but after therapy the PSR differed significantly between the subgroups [1.69 μmol/min.l (range 0.63-2.78) for NSCLC vs 0.67 μmol/min.l (range 0.45-0.92) for SCLC; P=0.03], irrespective of the treatment modality. The median SUV of tumour tissue was higher than that in corresponding contralateral normal lung both before and after therapy. Only a weak correlation between PSR and SUV was found when the latter was corrected for body surface area or lean body mass. Carbon-11 labelled tyrosine appears to be a good tracer for visualising lung cancer. PSR of tumour tissue can be used to quantify reduction in the metabolic rate of the tumour. Future studies need to be performed to determine whether TYR PET will supply additional clinical information with treatment implications in patients with lung cancer. (orig.)

  3. Pet Health

    Science.gov (United States)

    ... of safety to your life. Before getting a pet, think carefully about which animal is best for your family. What is each family member looking for in a pet? Who will take care of it? Does anyone ...

  4. New developments in radiotracers for PET

    International Nuclear Information System (INIS)

    PET (Positron Emission Tomography) is a medical imaging method in which a radiotracer tagged with a short-lived positron emitting isotope is used to track a specific biochemical process or the distribution and kinetics of a drug in a living human or animal subject. PET can be applied to an almost limitless variety of problems in biology and medicine because of the chemical flexibility of positron emitters such as carbon-11 (half-life: 20.4 min) and fluorine-18 (half-life: 110 min). Today radiotracers have been developed for probing a diversity of biochemical transformations including blood flow, sugar metabolism, neurotransmission and enzyme activity. In addition PET is finding increasing application in the study of therapeutic drugs and substances of abuse. Dopamine metabolism has been an area of intense interest because of derangements in diseases such as schizophrenia and Parkinson's disease. This has been probed from a number of perspectives with carbon-11 and fluorine-18 labeled tracers which participate selectively in dopamine metabolism, or bind to the dopamine reuptake system or post-synaptic receptors. Advances in the design of highly selective radiotracers, in rapid organic synthesis and sophisticated analytical methods and in mechanistic biochemical studies in vivo have all contributed to the advancement of PET and to its application to new problems in basic and clinical research

  5. Pet Health

    Science.gov (United States)

    Pets can add fun, companionship and a feeling of safety to your life. Before getting a pet, think carefully about which animal is best for ... is each family member looking for in a pet? Who will take care of it? Does anyone ...

  6. Development of new and improved labelling procedures for introducing isotopic hydrogen and carbon-11 into organic compounds

    International Nuclear Information System (INIS)

    New and improved methods for introducing radioisotopic hydrogen (tritium) and carbon (positron-emitting short-lived carbon-11, t1/2 = 20.4 min) into organic molecules for application in biological research have been explored. In Chapter 1 the applications of radioactive isotopes in biological and clinical research is surveyed, with particular emphasis on the value of β-emitting tritium and positron-emitting carbon-11. In Chapter 2 we report the use of the non-radioactive hydrogen isotope, deuterium, as a surrogate for tritium in the development of microwave-enhanced labelling procedures, based on catalytic hydrogen transfer to olefins (e.g. styrene, styrene derivatives, cinnamic acid and its derivatives). Hydrogen or deuterium donors (e.g. formate salts) were used alone or in combination with other sources (e.g. D2O). The method was found to give fully hydrogenated products using very short microwave irradiation times (∼ 2 min) and was highly reproducible. Importantly, the method is environmentally clean, as when extended to tritiated formates little or no radioactive waste is produced. In Chapter 3 we explored the labelling of CGP 62349 {3-[1-(R)-[3-(4-methoxybenzyl)phosphinyl-2-(S)-hydroxy-propyl- amino]ethyl]benzoic acid}, a γ-aminobutyric acid type B (GABAB) receptor antagonist, with carbon-11 in order to provide a prospective radioligand for medical imaging with positron emission tomography (PET). Labelling agents, [11C]iodomethane and [11C]methyl triflate, prepared by improved methods, were used in the rapid methylation of desmethyl-CGP 62349. Substantially higher radiochemical yields (78%) of [11C]CGP 62349 were achieved by the new methods compared to that produced in a previously published procedure (9%). In addition, the use of [11C]methyl triflate rather than [11C]iodomethane has the advantage of giving a high radiochemical yield and a lower amount of carrier. In Chapter 4 we report on the use of [11C]carbon monoxide as a labelling agent. This has

  7. The dynamics of methionine supply and demand during early development.

    Science.gov (United States)

    McBreairty, Laura E; Bertolo, Robert F

    2016-06-01

    Methionine is an indispensable amino acid that, when not incorporated into protein, is converted into the methyl donor S-adenosylmethionine as entry into the methionine cycle. Following transmethylation, homocysteine is either remethylated to reform methionine or irreversibly trans-sulfurated to form cysteine. Methionine flux to transmethylation and to protein synthesis are both high in the neonate and this review focuses on the dynamics of methionine supply and demand during early development, when growth requires expansion of pools of protein and transmethylation products such as creatine and phosphatidylcholine (PC). The nutrients folate and betaine (derived from choline) donate a methyl group during remethylation, providing an endogenous supply of methionine to meet the methionine demand. During early development, variability in the dietary supply of these methionine cycle-related nutrients can affect both the supply and the demand of methionine. For example, a greater need for creatine synthesis can limit methionine availability for protein and PC synthesis, whereas increased availability of remethylation nutrients can increase protein synthesis if dietary methionine is limiting. Moreover, changes to methyl group availability early in life can lead to permanent changes in epigenetic patterns of DNA methylation, which have been implicated in the early origins of adult disease phenomena. This review aims to summarize how changes in methyl supply and demand can affect the availability of methionine for various functions and highlights the importance of variability in methionine-related nutrients in the infant diet. PMID:27177124

  8. Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Wolf, A.P.

    1981-01-01

    A number of reviews, many of them recent, have appeared on various aspects of /sup 11/C, /sup 18/F and /sup 13/N-labeled radiotracers. This monograph treats the topic principally from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. Where possible, recent examples from the literature of organic synthesis are introduced to suggest potentially new routes which may be applied to problems in labeling organic molecules with the short-lived positron emitters, carbon-11, fluorine-18, and nitrogen-13. The literature survey of carbon-11, fluorine-18 and nitrogen-13 labeled compounds presented are of particular value to scientists working in this field. Two appendices are also included to provide supplementary general references. A subject index concludes this volume.

  9. Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications

    International Nuclear Information System (INIS)

    A number of reviews, many of them recent, have appeared on various aspects of 11C, 18F and 13N-labeled radiotracers. This monograph treats the topic principally from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. Where possible, recent examples from the literature of organic synthesis are introduced to suggest potentially new routes which may be applied to problems in labeling organic molecules with the short-lived positron emitters, carbon-11, fluorine-18, and nitrogen-13. The literature survey of carbon-11, fluorine-18 and nitrogen-13 labeled compounds presented are of particular value to scientists working in this field. Two appendices are also included to provide supplementary general references. A subject index concludes this volume

  10. Differential labeling of methionine with technetium-99m using chelation and trans-chelation: Can it be used for brain tumor imaging in developing countries

    International Nuclear Information System (INIS)

    A protein synthesis marker 11C-methionine-PET was used in differentiating residual post-radiotherapeutic viability and to differentiate the low-grade proliferating glioma with glioblastoma, SPECT facility has wider availability and reports with 201Thallium indicated that it can differentiate recurrence from necrosis. Since 11C and 201Thallium are cyclotron produced isotopes and in underdeveloped / developing countries, non-availability of cyclotron, PET cameras and their costing are the main constraints. With this aim studies were undertaken to label Methionine with technetium-99m for its possible use in brain tumor imaging. The l, methionine, was labeled with Technetium-99m after modifiying certain steps as reported by Tubis et al, and also by transchelating using a weak prochelator glucoheptonate. The labeling efficiencies were in order of 99 % and 97 % with chelating and transchelating mehods. In our studies we found that Tc-99m Methionine SPECT images are comparable with 11C - methionine PET images. The Methionine uptake index was calculated by drawing ROI around the tumor in the slice showing maximum activity and obtaining the counts. To know the background counts a similar ROI was drawn on the contra lateral side/lobe. The ratio of the two was obtained. The ratio as calculated in order of 6.0 and 8.2 for higher grade and low-grade glioma, respectively. The studies conducted so far in 150 patients indicated that this technology could be utilized further to (a) grading gliomas and (b) differentiating glioma from non-tumoral lesions and radiation necrosis.

  11. Simultaneous PET/MR imaging in a human brain PET/MR system in 50 patients-Current state of image quality

    Energy Technology Data Exchange (ETDEWEB)

    Schwenzer, N.F., E-mail: nina.schwenzer@med.uni-tuebingen.de [Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Tuebingen (Germany); Stegger, L., E-mail: stegger@gmx.net [Department of Nuclear Medicine and European Institute for Molecular Imaging, University of Muenster, Muenster (Germany); Bisdas, S., E-mail: sbisdas@gmail.com [Department of Diagnostic and Interventional Neuroradiology, Eberhard-Karls University Tuebingen, Tuebingen (Germany); Schraml, C., E-mail: christina.schraml@med.uni-tuebingen.de [Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Tuebingen (Germany); Kolb, A., E-mail: armin.kolb@med.uni-tuebingen.de [Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Preclinical Imaging and Radiopharmacy, Eberhard-Karls University Tuebingen, Tuebingen (Germany); Boss, A., E-mail: Andreas.Boss@usz.ch [Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Tuebingen (Germany); Institute of Diagnostic and Interventional Radiology, University Hospital Zuerich, Zuerich (Switzerland); Mueller, M., E-mail: mark.mueller@med.uni-tuebingen.de [Department of Nuclear Medicine, Eberhard-Karls University Tuebingen, Tuebingen (Germany); and others

    2012-11-15

    Objectives: The present work illustrates the current state of image quality and diagnostic accuracy in a new hybrid BrainPET/MR. Materials and methods: 50 patients with intracranial masses, head and upper neck tumors or neurodegenerative diseases were examined with a hybrid BrainPET/MR consisting of a conventional 3T MR system and an MR-compatible PET insert. Directly before PET/MR, all patients underwent a PET/CT examination with either [{sup 18}F]-FDG, [{sup 11}C]-methionine or [{sup 68}Ga]-DOTATOC. In addition to anatomical MR scans, functional sequences were performed including diffusion tensor imaging (DTI), arterial spin labeling (ASL) and proton-spectroscopy. Image quality score of MR imaging was evaluated using a 4-point-scale. PET data quality was assessed by evaluating FDG-uptake and tumor delineation with [{sup 11}C]-methionine and [{sup 68}Ga]-DOTATOC. FDG uptake quantification accuracy was evaluated by means of ROI analysis (right and left frontal and temporo-occipital lobes). The asymmetry indices and ratios between frontal and occipital ROIs were compared. Results: In 45/50 patients, PET/MR examination was successful. Visual analysis revealed a diagnostic image quality of anatomical MR imaging (mean quality score T2 FSE: 1.27 {+-} 0.54; FLAIR: 1.38 {+-} 0.61). ASL and proton-spectroscopy was possible in all cases. In DTI, dental artifacts lead to one non-diagnostic dataset (mean quality score DTI: 1.32 {+-} 0.69; ASL: 1.10 {+-} 0.31). PET datasets of PET/MR and PET/CT offered comparable tumor delineation with [{sup 11}C]-methionine; additional lesions were found in 2/8 [{sup 68}Ga]-DOTATOC-PET in the PET/MR. Mean asymmetry index revealed a high accordance between PET/MR and PET/CT (1.5 {+-} 2.2% vs. 0.9 {+-} 3.6%; mean ratio (frontal/parieto-occipital) 0.93 {+-} 0.08 vs. 0.96 {+-} 0.05), respectively. Conclusions: The hybrid BrainPET/MR allows for molecular, anatomical and functional imaging with uncompromised MR image quality and a high accordance

  12. Lung PET scan

    Science.gov (United States)

    Chest PET scan; Lung positron emission tomography; PET - chest; PET - lung; PET - tumor imaging ... A PET scan requires a small amount of tracer. The tracer is given through a vein (IV), usually on ...

  13. Performance of broilers fed with different levels of methionine hydroxy analogue and DL-methionine

    Directory of Open Access Journals (Sweden)

    Meirelles HT

    2003-01-01

    Full Text Available One-day-old male Ross chicks were used in an experiment designed to compare two methionine sources, DL-methionine and methionine hydroxy analogue free acid (MHA-FA, and four different levels: 0.41; 0.47; 0.53; 0.59% (starter diet; 0.35; 0.41; 0.47; 0.53% (grower diet; and 0.30; 0.36; 0.42; 0.48% (finisher diet. One thousand two hundred and eighty chicks were housed in 32 experimental floor-pens (40 birds each and fed 8 experimental diets based on corn and soybean meal for 47 days. The effects of methionine sources and levels were evaluated by performance data, carcass and cut yields, feather yield and abdominal fat content. Data were analyzed as a completely randomized design in a 2x4 factorial arrangement (2 sources and 4 levels, with 8 treatments and 4 repetitions. Analysis of variance was performed using PROC GLM of SAS©. Data indicated DL-methionine to be more effective in promoting growth than MHA-FA, and weight gain increased numerically in response to increasing levels of methionine in all phases.

  14. Imaging spectrum and pitfalls of {sup 11}C-methionine position emission tomography in a series of patients with intracranial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Kimiteru [Dept. of Radiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo (Japan); Matsuda, Hiroshi [Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Kubota, Kazoo [Div. of Nuclear Medicine, National Center for Global Health and Medicine, Tokyo (Japan)

    2016-06-15

    {sup 11}C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of {sup 11}C-Met PET for general practitioners. Physiological {sup 11}C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during {sup 11}C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of {sup 11}C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of {sup 11}C-Met images could help prevent unfavorable clinical results caused by misdiagnoses.

  15. Simultaneous PET/MR body imaging in rats. Initial experiences with an integrated PET/MRI scanner

    International Nuclear Information System (INIS)

    We recently developed an integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) (iPET/MRI) scanner for small animals, which had relatively large field-of-view (FOV) covering up to the size of a rat body. The purpose of this study was to report results of simultaneous PET/MRI of a rat body using this scanner with some radiotracers. C-11-methionine (MET), F-18-fluorodeoxyglucose (FDG), or F-18-sodium fluoride (NaF) was injected as a radiotracer for PET portion in addition to gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid, a hepatobiliary contrast agent, for MRI portion. Simultaneous PET/MRI was performed in normal rats. PET, MRI, and co-registered fusion images were evaluated regarding image quality and feasibility for rat imaging studies. MET uptake was clearly shown in the liver and pancreas, which was confirmed with magnetic resonance (MR) and fused PET/MR images. PET/MR images depicted intense FDG uptake in the brain, Harderian glands, and myocardium. NaF uptake was observed in all bones and joints within FOV, except in ribs, which was well recognized with the help of MR and fused PET/MR images. This study demonstrated that simultaneous PET/MRI with an integrated dual-modality molecular imaging scanner was a feasible technique for imaging studies targeting on a rat body. However, further developments including attenuation correction methods are required to use this technique routinely in rat imaging studies. (author)

  16. Methionine metabolism in apple tissue: implications of S-adenosylmethionine as an intermediate in the conversion of methionine to ethylene

    International Nuclear Information System (INIS)

    If S-adenosylmethionine (SAM) is the direct precursor of ethylene as previously proposed, it is expected that 5'-S-methyl-5'-thioadenosine (MTA) would be the fragment nucleoside. When [Me-14C] or (35S)methionine was fed to climacteric apple (Malus sylvestris Mill) tissue, radioactive 5-S-methyl-5-thioribose (MTR) was identified as the predominant product and MTA as a minor one. When the conversion of methionine into ethylene was inhibited by L-2-amino-4-(2'-amino-ethoxy)-trans-3-butenoic acid, the conversion of (35S) or (Me-14C)methionine into MTR was similarly inhibited. Furthermore, the formation of MTA and MTR from (35S)methionine was observed only in climacteric tissue which produced ethylene and actively converted methionine to ethylene but not in preclimacteric tissue which did not produce ethylene or convert methionine to ethylene. These observations suggest that the conversion of methionine into MTA and MTR is closely related to ethylene biosynthesis and provide indirect evidence that SAM may be an intermediate in the conversion of methionine to ethylene. When (35S)MTA was fed to climacteric or preclimacteric apple tissue, radioactivity was efficiently incorporated into MTR and methionine. However, when (35S)MTR was administered, radioactivity was efficiently incorporated into methionine but not MTA. A scheme is presented for the production of ethylene from methionine

  17. Efficiency of Positron Emission Tomography with 18F-Fluorodeoxyglucose, 11С-Methionine and 82Rb-Chloride in Differential Diagnosis of Lung Tumors and Some Inflammatory Pulmonary Diseases

    Directory of Open Access Journals (Sweden)

    Tlostanova М.S.

    2014-09-01

    Full Text Available The aim of the investigation was to study the informativeness of positron emission tomography (PET using 18F-FDG, 11С-methionine and 82Rb-chloride in differential diagnosis of tumor and some inflammatory pulmonary diseases. Materials and Methods. PET findings of 378 patients with lung tumors and inflammatory pulmonary diseases were studied. PET with 18F-FDG and 11С-methionine were performed 120 and 15 min, respectively, after their intravenous administration. PET with 82Rb-chloride was performed 1 min after distant intravenous administration. Quantitative processing of PET findings regardless the medication used included visual image analysis and calculation of Standardized Uptake Value (SUV in healthy pulmonary parenchyma and in lesion. Results. SUV in patients with lung cancer in PET with 18F-FDG and 11С-methionine were higher than metabolic activity in an inflammation region, while in PET with 82Rb-chloride, SUV levels were significantly higher in the foci of inflammation than in malignant tumors. The patients with benign tumors and most patients with focal pneumofibrosis in pulmonary tissue consolidation area were recorded to have background distribution of radiopharmaceuticals. It enabled to reliably differentiate benign tumors and focal pneumofibrosis from lung cancer regardless the medications used. Conclusion. The obtained data on the informativeness of positron emission tomography performed using 11С-methionine suggest high diagnostic value of the technique in the differential diagnosis of lung cancer, neuroendocrine tumors, benign tumors and inflammatory diseases. Despite good imaging potential PET with 82Rb-chloride is unreasonable in differentiation of lung tumors and inflammatory pulmonary diseases.

  18. Methionine metabolism after portacaval shunt in the rat

    International Nuclear Information System (INIS)

    The effect of portacaval shunt (PCS) on methionine metabolism in the rat was investigated. Male Sprague-Dawley rats were subjected to PCS and maintained on an 18% casein diet. Growth curves of operated rats were similar to controls. PCS rats excreted more urinary 35SO4 and less [35S]taurine than controls after intraperitoneal injection of 0.3 mmol/100 g [35S]methionine or [35S]cysteine. Total urinary taurine excretion was similar in PCS and control rats after a methionine or cysteine load; however, under basal conditions PCS rats had higher urinary taurine levels than controls, indicating that PCS may cause the taurine pool to be expanded. Hepatic methionine, S-adenosylmethionine, and cysteine pools were significantly decreased in PCS rats, while S-adenosylhomocysteine levels were unchanged. Relative rates of transsulfuration in PCS and control rats were studied by following the decrease in the 3H-to-35S ratio in liver protein after injection of [methyl-3H]methionine and [35S]methionine, and no difference in flux of 35S from [35S]methionine to [35S]cysteine was found. Similarly, total hepatic activities of methionine adenosyltransferase, cystathionine synthase, and cystathionine gamma-lyase were unchanged in PCS rats. These results indicate that altered methionine metabolism in PCS rats is not explained by changes in conversion of methionine to cysteine via the transsulfuration pathway

  19. Carbon 11-MPTP: a potential tracer for Parkinson's disease research in laboratory animals

    International Nuclear Information System (INIS)

    [11C]-1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ([11C]MPTP), a compound producing parkinson-like symptoms in several species, has been synthesized and purified in sufficient activity to obtain tomographic images in the monkey. Biodistribution data has also been obtained in rats. Carbon-11-labeled MPTP could be used as a probe to study the pharmacokinetics of the compound under various research conditions in animals. Because of its neurotoxicity, the compound is not intended for use in humans

  20. Bacterial variations on the methionine salvage pathway

    Directory of Open Access Journals (Sweden)

    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  1. N-Terminal methionine processing by the zinc-activated Plasmodium falciparum methionine aminopeptidase 1b.

    Science.gov (United States)

    Calcagno, Sarah; Klein, Christian D

    2016-08-01

    The methionine aminopeptidase 1b from Plasmodium falciparum (PfMetAP 1b) was cloned, expressed in Escherichia coli and characterized. Surprisingly, and in contrast to other methionine aminopeptidases (MetAPs) that require heavy-metal cofactors such as cobalt, the enzyme is reliably activated by zinc ions. Immobilization of the enzyme is possible by His-tag metal chelation to iminodiacetic acid-agarose and by covalent binding to chloroacetamido-hexyl-agarose. The covalently immobilized enzyme shows long-term stability, allowing a continuous, heterogenous processing of N-terminal methionines, for example, in recombinant proteins. Activation by zinc, instead of cobalt as for other MetAPs, avoids the introduction of heavy metals with toxicological liabilities and oxidative potential into biotechnological processes. The PfMetAP 1b therefore represents a useful tool for the enzymatic, posttranslational processing of recombinant proteins. PMID:27023914

  2. Syntheses of carbon-11 labeled piperidine esters as potential in vivo substrates for acetylcholinesterase

    International Nuclear Information System (INIS)

    A series of carbon-11 labeled N-methylpiperidinyl esters were prepared as potential in vivo substrates for acetylcholinesterase (AChE). Target compounds were designed based on the structure of N-[11C]methylpiperidin-4-yl propionate, an ester currently used to measure AChE enzymatic activity in the human brain, to examine the structure-activity relationship for in vivo enzymatic hydrolysis. Changes in steric bulk and in the ester order ('reverse' esters) were made. Addition of methyl groups was made to both the acid side chain (synthesis of N-[11C]methylmethylpiperidin-4-yl isobutyrate) and to the piperidine ring (syntheses of N-[11C]methyl-4-methylpiperidin-4-yl propionate, N-[11C]methyl-4-methylpiperidin-4-yl acetate, and N-[11C]methyl-3-methylpiperidin-4-yl propionate). Alterations of the order of the ester heteroatoms was accomplished through syntheses of the N-[11C]methyl-2,3- and 4-piperidinecarboxylic acid ethyl esters. Finally, an additional piperidine-based ester (N-[11C]methylpiperidin-2-yl)methyl propionate was also prepared. All carbon-11-labeled esters were prepared by N-[11C]methylation reactions, using the desmethyl precursors and no-carrier-added [11C]methyltriflate, and were obtained in decay-corrected yields (not optimized) of 10-40% and high specific activities

  3. Diabetic Pets

    Science.gov (United States)

    ... health or management, contact your veterinarian. In addition, diabetic pets should be monitored for long-term complications such as cataracts, which commonly develop in diabetic dogs and cats. Other problems that can occur ...

  4. Senior Pets

    Science.gov (United States)

    ... Future AVMA Meeting Dates Meetings & CE Calendar Symposiums & Summits Pet Health Awareness Events About AVMA Who We ... and small dogs are generally considered “senior” at seven years of age. Larger breed dogs tend to ...

  5. Formation of ethylene from methionine. Reactivity of radiolytically produced oxygen radicals and effect of substrate activation

    International Nuclear Information System (INIS)

    Ethylene was determined by gas chromatography after reaction of radiolytically produced OH and 02- radicals with methionine, methionine + pyridoxal phosphate and S-adenosyl-methionine (SAM). Both oxygen radicals, alone or in combination, liberate ethylene from methionine and methionine/pyridoxal phosphate. From SAM ethyline was primarily produced by the combined attack of OH and H202 or 02-. (author)

  6. Comparison of methionine sources around requirement levels using a methionine efficacy method in 0 to 28 day old broilers.

    Science.gov (United States)

    Agostini, P S; Dalibard, P; Mercier, Y; Van der Aar, P; Van der Klis, J D

    2016-03-01

    The addition of methionine in the poultry feed industry is still facing the relative efficacy dilemma between DL-methionine (DLM) and hydroxy-methionine (HMTBA). The aim of this study was to compare the effect of dietary DLM and HMTBA on broiler performance at different levels of total sulfur amino acids (TSAA). The treatments consisted of a basal diet without methionine addition, and 4 increasing methionine doses for both sources resulting in TSAA/Lysine ratios from 0.62 to 0.73 in the starter phase and 0.59 to 0.82 in the grower phase. The comparison of product performance was performed by three-way ANOVA analysis and by methionine efficacy calculation as an alternative method of comparison. Growth results obtained during the starter phase with the different methionine supplementations did not show significant growth responses to TSAA levels, indicating a lower methionine requirement in the starter phase than currently assumed. However, a significant methionine dose effect was obtained for the period 10 to 28 day of age and for the entire growth period of 0 to 28 day of age. Excepting a significant gender effect, the statistical analysis did not allow for the discrimination of methionine sources, and no interaction between source and dose level was observed up to 28 days of age. A significant interaction between source and dose level was observed for methionine efficacy for the grower phase, and the total growth period showed better HMTBA efficacy at higher TSAA value. The exponential model fitted to each methionine source for body weight response depending on methionine intake or for feed conversion ratio (FCR) depending on methionine doses did not allow the methionine sources to be distinguished. Altogether, these results conclude that methionine sources lead to similar performances response when compared at TSAA values around the broiler requirement level. These results also showed that at TSAA values above requirement, HMTBA had a better methionine efficacy

  7. S-adenosyl-L-methionine for alcoholic liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed the ...... question whether SAMe may benefit patients with alcoholic liver diseases.......Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed the...

  8. Positron Emission Tomography (PET)

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs

  9. Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, P. [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot; Hospital Garcia de Orta, Servico de Medicina Nuclear, Pragal, Almada (Portugal); Ribeiro, M.J. [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot; Servico de Biofisica, IBILI, Faculdade de Medicina de Coimbra (Portugal); Bottlaender, M.; Loc' h, C.; Langer, O.; Strul, D.; Maziere, B.; Bendriem, B. [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot; Hugonnard, P.; Grangeat, P. [CEA Centre d' Etudes Nucleaires de Grenoble, 38 (France). Lab. d' Electronique de Technologie et d' Instrumentation

    1999-12-01

    Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D{sub 2} receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using {sup 123}I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 ), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of {sup 123}I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to {sup 123}I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a {sup 123}I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC+AT) and (SC+CBC+AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of {sup 11}C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (%ID/100 ml) obtained after (SC+CBC+AT) in SPET are in good agreement with those obtained with PET and {sup 11}C-epidepride. A method for the in vivo

  10. Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography.

    Science.gov (United States)

    Almeida, P; Ribeiro, M J; Bottlaender, M; Loc'h, C; Langer, O; Strul, D; Hugonnard, P; Grangeat, P; Mazière, B; Bendriem, B

    1999-12-01

    Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123

  11. Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

    International Nuclear Information System (INIS)

    Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 ), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC+AT) and (SC+CBC+AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (%ID/100 ml) obtained after (SC+CBC+AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I

  12. PET/CT in radiation therapy planning

    International Nuclear Information System (INIS)

    Regarding treatment planning in radiotherapy PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, following experimental, clinical and cost/benefit analysis are required. FDG-PET has a significant impact on GTV and PTV delineation in lung cancer and can detect lymph node involvement and differentiation of malignant tissue from atelectasis. In high-grade gliomas and meningiomas, methionine-PET helps to define the GTV and differentiate tumor from normal tissue. In head and neck cancer, cervix cancer and prostate cancer the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET can be superior to CT and MRI in the detection of lymph node metastases in head and neck, unknown primary cancer and differentiation of viable tumor tissue after treatment. Therefore, it could play an important role in GTV definition and sparing of normal tissue. For other entities like gastro-intestinal cancer, lymphomas, sarcoma etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can be individually targeted using IMRT. In addition, a biological dose distribution can be generated, the so-called dose painting. However, systematical experimental and clinical trials are necessary to validate this hypothesis. (orig.)

  13. Non-FDG PET in the practice of oncology

    OpenAIRE

    P Caroli; C. Nanni; Rubello, D; A. Alavi; S. Fanti

    2010-01-01

    Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET...

  14. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin;

    2012-01-01

    neurobiology and eventual dysfunctions of the 5-HT(7) receptor. To date, no appropriate 5-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT...

  15. False positive localisation of C-11 methionine in a colloid nodule

    International Nuclear Information System (INIS)

    A 45-year-old female diagnosed with carcinoma of the left breast on histopathological examination underwent both 18F-flourodeoxyglucose (FDG) and 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) as part of a protocol comparing the utility of these tracers for predicting a response to neoadjuvant chemotherapy in breast carcinoma. Abnormal FDG and MET accumulation was noted in the left breast primary, left axillary lymph nodes, and also in a well-defined nodule present in the left lobe of the thyroid gland. Keeping in mind the possibility of thyroid neoplasm/metastasis, the patient was referred for fine needle aspiration cytology (FNAC) from the thyroid nodule that revealed features of a simple colloid nodule. Focal thyroid lesions incidentally found on 18F-FDG PET/CT have a high risk of thyroid malignancy. Non-specific accumulation of FDG in thyroid adenomas is also known. This case highlights a potential cause for false positive on C-11 MET PET/CT in colloid adenomas, which should be kept in mind while using this tracer for oncological indications

  16. Advances in Bacterial Methionine Aminopeptidase Inhibition.

    Science.gov (United States)

    Helgren, Travis R; Wangtrakuldee, Phumvadee; Staker, Bart L; Hagen, Timothy J

    2016-01-01

    Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal structures of bacterial MetAPs are deposited into the PDB. This review highlights the available crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development of potential antibacterial agents. PMID:26268344

  17. High Methionine Diet Poses Cardiac Threat: A Molecular Insight.

    Science.gov (United States)

    Chaturvedi, Pankaj; Kamat, Pradip K; Kalani, Anuradha; Familtseva, Anastasia; Tyagi, Suresh C

    2016-07-01

    High methionine diet (HMD) for example red meat which includes lamb, beef, pork can pose cardiac threat and vascular dysfunction but the mechanisms are unclear. We hypothesize that a diet rich in methionine can malfunction the cardiovascular system in three ways: (1) by augmenting oxidative stress; (2) by inflammatory manifestations; and (3) by matrix/vascular remodeling. To test this hypothesis we used four groups of mice: (1) WT; (2) WT + methionine; (3) CBS(+/-) ; (4) CBS(+/-) +methionine. We observed high oxidative stress in mice fed with methionine which was even higher in CBS(+/-) and CBS(+/-) +methionine. Higher oxidative stress was indicated by high levels of SOD-1 in methionine fed mouse hearts whereas IL-1β, IL-6, TNFα, and TLR4 showed high inflammatory manifestations. The upregulated levels of eNOS/iNOS and upregulated levels of MMP2/MMP9 along with high collagen deposition indicated vascular and matrix remodeling in methionine fed mouse. We evaluated the cardiac function which was dysregulated in the mice fed with HMD. These mice had decreased ejection fraction and left ventricular dysfunction which subsequently leads to adverse cardiac remodeling. In conclusion, our study clearly shows that HMD poses a cardiac threat by increasing oxidative stress, inflammatory manifestations, matrix/vascular remodeling, and decreased cardiac function. J. Cell. Physiol. 231: 1554-1561, 2016. © 2015 Wiley Periodicals, Inc. PMID:26565991

  18. Radiopharmaceutical production for PET: Quality assurance, practice, experiences and issues

    International Nuclear Information System (INIS)

    The half-lives of the positron-emitting radioisotopes, carbon-11 (t1/2 = 20.3 min) and fluorine-18 (t1/2 = 109.6 min), preclude lengthy techniques from the routine analysis of radiopharmaceuticals derived for positron emission tomography (PET). Therefore, the assurance of radiopharmaceutical quality, with respect to safety and efficacy, should rely heavily on establishing a well-defined production protocol that delivers a high quality product from materials of specified grade. Also, this protocol should be supported routinely by rapid quality control procedures. Such a combination constitutes good manufacturing practice (GMP) in radiopharmaceutical production for PET. This talk will describe the application of GMP, in a PET centre regularly producing a wide range of 11C- and 18F-radiopharmaceuticals

  19. Atmospheric tracer study of the emissions from the University of Michigan Cyclotron/PET Facility

    International Nuclear Information System (INIS)

    The University of Michigan (U of M) Cyclotron/Positron Emission Tomography (PET) facility consists of a cyclotron (Model CS-30, The Cyclotron Corporation), radiochemistry laboratory, and Pet scanner. Accelerator-produced radioactive materials, such as, carbon-11 and oxygen-15 are typically emitted from the Cyclotron/PET facility through short stacks located on the roof. This project studied the dispersion of emissions from the facility within the medical complex. To achieve this purpose, the research project had three phases: a physical modeling study; a preliminary field smoke release study; and, a field study using a tracer gas to simulate emission dispersion from the U of M Cyclotron/PET facility vault stack. The objective was to determine normalized concentrations, under selected wind directions and speeds, for use in establishing radionuclide concentrations at the air intakes of the Cyclotron/PET facility and surrounding buildings and at selected ground-level locations

  20. Cyclotron-produced radioisotopes and their clinical use at the Austin PET Centre

    Energy Technology Data Exchange (ETDEWEB)

    Tochon-Danguy, H.J. [Centre for PET, Melbourne, VIC (Australia). Austin and Repatriation Medical Centre

    1997-12-31

    A Centre for Positron Emission Tomography (PET) has been established within the Department of Nuclear Medicine at the Austin and Repatriation Medical Centre in Melbourne. PET is a non-invasive technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic equipment consists of a medical cyclotron (10 MeV proton and 5 MeV deuteron), six lead-shielded hot cells with associated radiochemistry facilities and a whole body PET scanner. During its first five years of operation, the Melbourne PET Centre, has pursued a strong radiolabelling development program, leading to an ambitious clinical program in neurology, oncology and cardiology. This presentation will describe the basic principles of the PET technique and review the cyclotron-produced radioisotopes and radiopharmaceuticals. Radiolabelling development programs and clinical applications are also addressed. 30 refs., 1 tab., 1 fig.

  1. Cyclotron-produced radioisotopes and their clinical use at the Austin PET Centre

    International Nuclear Information System (INIS)

    A Centre for Positron Emission Tomography (PET) has been established within the Department of Nuclear Medicine at the Austin and Repatriation Medical Centre in Melbourne. PET is a non-invasive technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic equipment consists of a medical cyclotron (10 MeV proton and 5 MeV deuteron), six lead-shielded hot cells with associated radiochemistry facilities and a whole body PET scanner. During its first five years of operation, the Melbourne PET Centre, has pursued a strong radiolabelling development program, leading to an ambitious clinical program in neurology, oncology and cardiology. This presentation will describe the basic principles of the PET technique and review the cyclotron-produced radioisotopes and radiopharmaceuticals. Radiolabelling development programs and clinical applications are also addressed

  2. Role of Methionine Adenosyltransferase Genes in Hepatocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ramani, Komal [Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, Southern California Research Center for Alcoholic Liver and Pancreatic Diseases & Cirrhosis, Keck School of Medicine USC, Los Angeles, California 90033 (United States); Mato, José M. [CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology, Park of Bizkaia, 48160 Derio, Bizkaia (Spain); Lu, Shelly C., E-mail: shellylu@usc.edu [Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, Southern California Research Center for Alcoholic Liver and Pancreatic Diseases & Cirrhosis, Keck School of Medicine USC, Los Angeles, California 90033 (United States)

    2011-03-24

    Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Detection of HCC can be difficult, as most of the patients who develop this tumor have no symptoms other than those related to their longstanding liver disease. There is an urgent need to understand the molecular mechanisms that are responsible for the development of this disease so that appropriate therapies can be designed. Methionine adenosyltransferase (MAT) is an essential enzyme required for the biosynthesis of S-adenosylmethionine (AdoMet), an important methyl donor in the cell. Alterations in the expression of MAT genes and a decline in AdoMet biosynthesis are known to be associated with liver injury, cirrhosis and HCC. This review focuses on the role of MAT genes in HCC development and the scope for therapeutic strategies using these genes.

  3. Role of Methionine Adenosyltransferase Genes in Hepatocarcinogenesis

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Detection of HCC can be difficult, as most of the patients who develop this tumor have no symptoms other than those related to their longstanding liver disease. There is an urgent need to understand the molecular mechanisms that are responsible for the development of this disease so that appropriate therapies can be designed. Methionine adenosyltransferase (MAT) is an essential enzyme required for the biosynthesis of S-adenosylmethionine (AdoMet), an important methyl donor in the cell. Alterations in the expression of MAT genes and a decline in AdoMet biosynthesis are known to be associated with liver injury, cirrhosis and HCC. This review focuses on the role of MAT genes in HCC development and the scope for therapeutic strategies using these genes

  4. SU-E-J-144: Low Activity Studies of Carbon 11 Activation Via GATE Monte Carlo

    International Nuclear Information System (INIS)

    Purpose: To investigate the behavior of a Monte Carlo simulation code with low levels of activity (∼1,000Bq). Such activity levels are expected from phantoms and patients activated via a proton therapy beam. Methods: Three different ranges for a therapeutic proton radiation beam were examined in a Monte Carlo simulation code: 13.5, 17.0 and 21.0cm. For each range, the decay of an equivalent length11C source and additional sources of length plus or minus one cm was studied in a benchmark PET simulation for activities of 1000, 2000 and 3000Bq. The ranges were chosen to coincide with a previous activation study, and the activities were chosen to coincide with the approximate level of isotope creation expected in a phantom or patient irradiated by a therapeutic proton beam. The GATE 7.0 simulation was completed on a cluster node, running Scientific Linux Carbon 6 (Red Hat©). The resulting Monte Carlo data were investigated with the ROOT (CERN) analysis tool. The half-life of11C was extracted via a histogram fit to the number of simulated PET events vs. time. Results: The average slope of the deviation of the extracted carbon half life from the expected/nominal value vs. activity showed a generally positive value. This was unexpected, as the deviation should, in principal, decrease with increased activity and lower statistical uncertainty. Conclusion: For activity levels on the order of 1,000Bq, the behavior of a benchmark PET test was somewhat unexpected. It is important to be aware of the limitations of low activity PET images, and low activity Monte Carlo simulations. This work was funded in part by the Philips corporation

  5. Pet Allergy Quiz

    Science.gov (United States)

    ... people with pet allergy do better with a dog that has short hair or sheds less. Question 2 Pet allergies are triggered by the hair on a pet. True False False: Pet allergies are caused by an allergen found on the pet’s skin (dander), saliva or urine. Question 3 Symptoms of pet allergy ...

  6. PET/CT in radiation therapy planning; PET/CT in der Strahlentherapieplanung

    Energy Technology Data Exchange (ETDEWEB)

    Grosu, A.L. [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Krause, B.J. [Klinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Nestle, U. [Klinik fuer Nuklearmedizin, Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany)

    2006-09-15

    Regarding treatment planning in radiotherapy PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, following experimental, clinical and cost/benefit analysis are required. FDG-PET has a significant impact on GTV and PTV delineation in lung cancer and can detect lymph node involvement and differentiation of malignant tissue from atelectasis. In high-grade gliomas and meningiomas, methionine-PET helps to define the GTV and differentiate tumor from normal tissue. In head and neck cancer, cervix cancer and prostate cancer the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET can be superior to CT and MRI in the detection of lymph node metastases in head and neck, unknown primary cancer and differentiation of viable tumor tissue after treatment. Therefore, it could play an important role in GTV definition and sparing of normal tissue. For other entities like gastro-intestinal cancer, lymphomas, sarcoma etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can be individually targeted using IMRT. In addition, a biological dose distribution can be generated, the so-called dose painting. However, systematical experimental and clinical trials are necessary to validate this hypothesis. (orig.)

  7. Radiation protection problems in a laboratory for the labelling of molecules with carbon-11

    International Nuclear Information System (INIS)

    This paper shows that the qualities of carbon-11, especially its short half-life, which suit it so well for the labelling of radiopharmaceuticals prove to be a great handicap in the preparation of these substances. The operator has to make a fresh preparation for each examination and start with strong radioactivities (200 to 500 mCi) in order to obtain an adequate injected activity at the end of the process, the absorbed dose averaging 1.5 man-rem per manipulation at the fingertips. The development of an automatic preparation method involving as little manual interference as possible has halved the collective dose for twice the dose handled. The labelling of molecules used for diagnosis is now considered to take place under satisfactory radioprotection conditions. The fingertip irradiations are analysed in the light of CIPR recommendations, while regretting that in publication 26 this problem of partial external irradiation of the skin is not dealt with as clearly and precisely as before

  8. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [11C]physostigmine

    International Nuclear Information System (INIS)

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [11C]methylisocyanate with eseroline. [11C]Methylisocyanate was obtained by heating [11C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [11C]CH3COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [11C]carbon dioxide and the addition of phthaloyl dichloride. The [11C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25oC, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [11C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [11C]Physostigmine are obtained 57 minutes after EOB. (author)

  9. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [[sup 11]C]physostigmine

    Energy Technology Data Exchange (ETDEWEB)

    Bonnot-Lours, S.; Crouzel, C.; Prenant, C.; Hinnen, F. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot)

    1993-01-01

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [[sup 11]C]methylisocyanate with eseroline. [[sup 11]C]Methylisocyanate was obtained by heating [[sup 11]C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [[sup 11]C]CH[sub 3]COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [[sup 11]C]carbon dioxide and the addition of phthaloyl dichloride. The [[sup 11]C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25[sup o]C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [[sup 11]C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [[sup 11]C]Physostigmine are obtained 57 minutes after EOB. (author).

  10. Design, Synthesis, and Evaluation of a Low-Molecular-Weight (11)C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry.

    Science.gov (United States)

    Denk, Christoph; Svatunek, Dennis; Mairinger, Severin; Stanek, Johann; Filip, Thomas; Matscheko, Dominik; Kuntner, Claudia; Wanek, Thomas; Mikula, Hannes

    2016-07-20

    A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal (11)C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this (11)C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time. PMID:27308894

  11. Interference by methionine on valine uptake in Acremonium chrysogenum.

    OpenAIRE

    Alonso, M J; Luengo, J M

    1987-01-01

    The incorporation of L-[U-14C]valine into delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), a direct biosynthetic precursor of penicillins and cephalosporins, was studied. When DL-methionine was added to Acremonium chrysogenum culture broths, no labeled ACV was found, while a large amount of radioactive ACV was detected when methionine was not present. DL-Norleucine, a nonsulfur analog of methionine, also inhibited the synthesis of radioactive ACV to some degree. This effect was due to ...

  12. Breast PET scan

    Science.gov (United States)

    Breast positron emission tomography; PET - breast; PET - tumor imaging - breast ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), usually ...

  13. Pet Care: MRSA FAQ

    Science.gov (United States)

    ... AVMA Meeting Dates Meetings & CE Calendar Symposiums & Summits Pet Health Awareness Events About AVMA Who We Are ... 12 Educators You are here: Home | Public Resources | Pet Care Print Share This! Your Veterinarian Pet Care ...

  14. Non-FDG PET in the practice of oncology

    Directory of Open Access Journals (Sweden)

    P Caroli

    2010-01-01

    Full Text Available Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the

  15. American Pet Culture

    Institute of Scientific and Technical Information of China (English)

    海焰

    2007-01-01

    In America you can find dogs,cats, horses,monkeys, snakes and even pigs in almost every family.They are their pets.Americans love pets and look on them as a part of the family.Sometimes pet owners dress their pets in fashionable clothes.They even buy toys for their pets.Americans love their pets as their children, sometimes even better.

  16. Conversion of Methionine to Thiols by Lactococci, Lactobacilli, and Brevibacteria†

    OpenAIRE

    Dias, Benjamin; Weimer, Bart

    1998-01-01

    Methanethiol has been strongly associated with desirable Cheddar cheese flavor and can be formed from the degradation of methionine (Met) via a number of microbial enzymes. Methionine γ-lyase is thought to play a major role in the catabolism of Met and generation of methanethiol in several species of bacteria. Other enzymes that have been reported to be capable of producing methanethiol from Met in lactic acid bacteria include cystathionine β-lyase and cystathionine γ-lyase. The objective of ...

  17. Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease1

    OpenAIRE

    Halsted, Charles H.; Medici, Valentina

    2011-01-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencie...

  18. Measurement of regional pulmonary function with carbon-11-labeled CO2 and CO

    International Nuclear Information System (INIS)

    Carbon dioxide and carbon monoxide labelled with carbon-11 have been produced in the remotecontrolled system for a large scale production of short lived radioactive substance with cyclotron in National Institute of Radiological Sciences. The single breath measurement with 11CO2 and 11CO, using inhalation system and a coincidence positron camera combined with an on-line computer system (TOSBAC 3400 Model 31) has been employed to evaluate regional pulmonary blood flow and diffusing capacity in three normal volunteers and seven patients with chronic obstructive pulmonary disease (COPD), old lung tuberculosis and benign tumor. Regional clearance rate constant (lambda) and distribution index (lambda i/lambda t) were calculated from monoexponential removal curves measured by external counting over the chest in supine position. This process was performed in a short period of breath-holding (10 - 20 sec.) after a single breath of these radioactive gases mixed with room air. These parameters were calculated for each lung fields divided into four zones (bilateral upper and lower lung region). In our method, the activity of the inspired mixture were 5 - 35 mCi/L and each value in lung fields, divided into four zones, can be measured with time interval for one second. While the clearance rate of 11CO2 seemed to be mainly limited by pulmonary blood flow, it was considered that the rate of 11CO were limited by not only the diffusing capacity but also the perfusion in each lung fields. In normal subjects, the distribution of regional clearance rate was showed approximately even for 11CO2 and 11CO. It was caused of the measurement in supine position. In contrast, the distribution of these parameter was showed uneven in patients with lung disease, particularly with COPD. (author)

  19. Methionine salvage pathway in relation to ethylene biosynthesis

    International Nuclear Information System (INIS)

    The recycling of methionine during ethylene biosynthesis (the methionine cycle) was studied. During ethylene biosynthesis, the H3CS-group of S-adenosylmethionine (SAM) is released at 5'-methylthioadenosine (MTA), which is recycled to methionine via 5'-methylthioribose (MTS). In mungbean hypocotyls and cell-free extracts of avocado fruit, [14C]MTR was converted to labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB) as intermediates. Radioactive tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract required an amino group donor. Among several potential donors tested, L-glutamine was the most efficient. Incubation of [ribose-U-14C]MTR with avocado extract resulted in the production of [14C]formate, with little evolution of other 14C-labeled one-carbon compounds, indicating that the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR

  20. Comparison of 99mTc-labeled methionine and 11C methionine radiotracer in the detection of breast carcinomas

    International Nuclear Information System (INIS)

    The cost effectiveness and non-availability of Cyclotron in underdeveloped and developing countries is a basic problem. Therefore studies were undertaken after labeling Methionine with generator produced Technetium-99m for its possible use in breast cancer imaging

  1. Pet Problems at Home: Pet Problems in the Community.

    Science.gov (United States)

    Soltow, Willow

    1984-01-01

    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  2. Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate--comparison between the normal and failing human heart.

    Science.gov (United States)

    Bengel, F M; Permanetter, B; Ungerer, M; Nekolla, S; Schwaiger, M

    2000-03-01

    The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET), can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with 11C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A "stroke work index" (SWI) was calculated by: SWI = systolic blood pressure x stroke volume/body surface area. To estimate myocardial efficiency, a "work-metabolic index" (WMI) was then obtained as follows: WMI = SWI x heart rate/k(mono), where k(mono) is the washout constant for 11C-acetate derived from monoexponential fitting. In DCM patients, left ventricular ejection fraction was 19%+/-10% and end-diastolic volume was 92+/-28 ml/m2 (vs 64%+/-7% and 55+/-8 ml/m2 in normals, PSWI (1674+/-761 vs 4736+/-895 mmHg x ml/m2; P<0.001) and the WMI as an estimate of efficiency (2.98+/-1.30 vs 6.20+/-2.25 x 10(6) mmHg x ml/m2; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=-0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=-0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart

  3. A Study on Pet Owners' Intention to Purchase Pet Insurance

    OpenAIRE

    Chiehwei Hung; Yen-Shan Chuang

    2014-01-01

    This study investigates the impacts of consumers¡¦ characteristics, pet feeding habits, pet spending and insurance conditions of pet owners on the intention to purchase a pet insurance policy. Our results reveal that family income, average monthly spending on pets, and experience of purchasing medical insurance are the significant determinants of a pet owner¡¦s intention to purchase pet insurance. Pet owners who have higher family income, higher pet spending, and who have previously purchased...

  4. PET studies of stroke

    International Nuclear Information System (INIS)

    PET already has been helpful in ischemic stroke disease. It has given us new data on physiological events occurring after a stroke; PET indices of blood flow and metabolism have provided the basis for staging the severity of tissue injury and predicting outcome, and PET has shown alterations in tissue function in response to therapy. Experience with PET in hemorrhagic disease is more limited, but initial results suggest a useful role for PET in the evaluation of nontraumatic intracranial hemorrhage as well [Ackerman et al., 1983a]. This brief review discusses general problems in the study of stroke disease using PET and then the contribution of PET to the stroke field

  5. Genetic engineering for high methionine grain legumes.

    Science.gov (United States)

    Müntz, K; Christov, V; Saalbach, G; Saalbach, I; Waddell, D; Pickardt, T; Schieder, O; Wüstenhagen, T

    1998-08-01

    Methionine (Met) is the primary limiting essential amino acid in grain legumes. The imbalance in amino acid composition restricts their biological value (BV) to 55 to 75% of that of animal protein. So far improvement of the BV could not be achieved by conventional breeding. Therefore, genetic engineering was employed by several laboratories to resolve the problem. Three strategies have been followed. A) Engineering for increased free Met levels; B) engineering of endogenous storage proteins with increased numbers of Met residues; C) transfer of foreign genes encoding Met-rich proteins, e.g. the Brazil nut 2S albumin (BNA) and its homologue from sunflower, into grain legumes. The latter strategy turned out to be most promising. In all cases the gene was put under the control of a developmentally regulated seed specific promoter and transferred into grain legumes using the bacterial Agrobacterium tumefaciens-system. Integration into and copy numbers in the plant genome as well as Mendelian inheritance and gene dosage effects were verified. After correct precursor processing the mature 2S albumin was intracellularly deposited in protein bodies which are part of the vacuolar compartment. The foreign protein amounted to 5 to 10% of the total seed protein in the best transgenic lines of narbon bean (Vicia narbonensis L., used in the authors' laboratories), lupins (Lupinus angustifolius L., used in CSIRO, Australia), and soybean (Glycine max (L.) Merr., used by Pioneer Hi-Bred, Inc., USA). In the narbon bean the increase of Met was directly related to the amount of 2S albumin in the transgenic seeds, but in soybean it remained below the theoretically expected value. Nevertheless, trangenic soybean reached 100%, whereas narbon bean and lupins reached approximately 80% of the FAO-standard for nutritionally balanced food proteins. These results document that the Met problem of grain legumes can be resolved by genetic engineering. PMID:9739551

  6. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk;

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  7. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lehberg; Afzelius, Pia; Bender, Dirk;

    2014-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  8. PET in Lung Cancer

    OpenAIRE

    Hans C. Steinert,

    2005-01-01

    Accurate tumor staging is essential for choosing the appropriate treatment strategy inpatients with lung cancer. It has already been shown that FDG-PET is highly accurate inclassifying lung nodules as benign or malignant. Integrated PET-CT enables the exactmatching of focal abnormalities on PET to anatomic structures on CT. PET-CT is superior indiagnostic accuracy for T staging and differentiation between tumor and peritumoral atelectasis.PET has also proved to be a very effective staging mod...

  9. Cyclotron, positrons and PET [positron emission tomography]. An overview

    International Nuclear Information System (INIS)

    PET (positron emission tomography) is a powerful new scientific tool which is capable of revealing biochemical transformations while they are occurring in the brain and other organs in the living human body. The application of PET to problems in biology and medicine is dominated by the short half-life of the isotopes used to prepare the radiotracers. The most commonly used positron emitting isotopes are carbon-11, fluorine-18, nitrogen-13, and oxygen-15 which have half-lives of 20.4, 110, 10 and 2 minutes, respectively. Their incorporation into radiotracers having diverse chemical structures and biochemical specificities has allowed the study of blood flow, sugar metabolism, oxygen metabolism, neurotransmission, enzyme activity and binding sites for therapeutic drugs and substances of abuse. PET research is most commonly carried out at a Cyclotron-PET Center (cyclotron, positron emission tomography, chemistry laboratory) where the short-lived isotopes can be produced and used efficiently. The number of Cyclotron-PET Centers has grown from 4 in 1976 to several dozen in 1988 and the number is expected to double in the next five years attesting to the vitality of the field and the current and anticipated contributions to research in biology and medicine

  10. Methionine metabolism and ethylene formation in etiolated pea stem sections

    International Nuclear Information System (INIS)

    Stem sections of etiolated pea seedlings (Pisum sativum L. cv. Alaska) were incubated overnight on tracer amounts of L-[U-14C]methionine and, on the following morning, on 0.1 millimolar indoleacetic acid to induce ethylene formation. Following the overnight incubation, over 70% of the radioactivity in the soluble fraction was shown to be associated with S-methylmethionine (SMM). The specific radioactivity of the ethylene evolved closely paralleled that of carbon atoms 3 and 4 of methionine extracted from the tissue and was always higher than that determined for carbon atoms 3 and 4 of extracted SMM. Overnight incubation of pea stem sections on 1 millimolar methionine enhanced indoleacetic acid-induced ethylene formation by 5 to 10%. Under the same conditions, 1 millimolar homocysteine thiolactone increased ethylene synthesis by 20 to 25%, while SMM within a concentration range of 0.1 to 10 millimolar did not influence ethylene production. When unlabeled methionine or homocysteine thiolactone was applied to stem sections which had been incubated overnight in L-[U-14C]methionine, the specific radioactivity of the ethylene evolved was considerably lowered. Application of unlabeled SMM reduced the specific radioactivity of ethylene only slightly

  11. A useful method to evaluate 11C-methionine uptake using positron emission tomography. Determination of the optimal scanning time for evaluation and a comparison between the tumor-to-muscle ratio and the distribution absorption ratio

    International Nuclear Information System (INIS)

    We determined the optimal scanning time for evaluating 11C-methionine uptake and then compared the usefulness of the tumor-to-muscle ratio (TMR) with the distribution absorption ratio (DAR) using positron emission tomography. Forty-two PET studies were performed to examine 42 tumorous lesions, 25 normal lung tissues, 23 normal bone marrow and 39 blood pool. In the 42 lesions examined, the TMR at 5, 10-20, 20-32 and 32-40 minutes after 11C-methionine injection, compared with that at 45-60 minutes, was 96±23%, 91±8.6%, 94±6.9% and 96±6.9%, respectively. A correlation study between the TMR and the DAR demonstrated good results in both the normal tissue (r=0.96) and the tumorous lesions (r=0.93). In conclusion, the 11C-methionine uptake can be evaluated at any time from 10 minutes after the injection of 11C-methionine and both the TMR and the DAR are considered to be useful methods for evaluating 11C-methionine uptake using positron emission tomography. (author)

  12. Fast high performance liquid chromatography in PET quality control metabolite analysis

    International Nuclear Information System (INIS)

    Quality control (Q C) and metabolite analysis on compounds labelled with positron emitting isotopes used for positron emission tomography (PET) studies are constrained by time. For carbon-11 labelled tracers, it is generally accepted that the Q C and subsequent release process should take no longer than 20 minutes to ensure both high product specific activity and activity in order to meet the aims of the studies in which it is used. From a regulatory point of view, PET manufacturing and associated Q C testing are increasingly expected to meet Good Manufacturing Practices (GMP) standards. The challenge for the PET Q C laboratory of today is to marry the requirement for fast testing with meeting applicable regulations and guidance. Although regulatory requirements are typically less of an issue for PET metabolite analysis, it has a significant impact on the ability to perform quantitative PET pharmacokinetic analysis on the acquired PET imaging data. This paper aims to provide a general overview and guidance on good practice for PET HPLC quality control and aims to highlight some recent developments that may aid in speeding up both PET Q C and metabolite HPLC analysis methods.

  13. Production and application of synthetic precursors labeled with carbon-11 and fluorine-18

    Energy Technology Data Exchange (ETDEWEB)

    Ferrieri, R.A.

    2001-04-02

    It is evident from this chapter that there is enormous flexibility both in the selection of the nature of the radioisotope and ways to generate it, as well as in the selection of the labeling precursor to appropriately attach that radioisotope to some larger biomolecule of interest. The arsenal of radiolabeling precursors now available to the chemist is quite extensive, and without a doubt will continue to grow as chemists develop new ones. However, the upcoming years will perhaps reflect a greater effort in refining existing methods for preparing some of those precursors that are already available to us. For example, the use of solid-phase reactions to accomplish in a single step what would normally take several using conventional solvent-based reactions has already been shown to work in many occasions. The obvious advantage here is that processes become more amenable to system automation thus affording greater reliability in day-to-day operations. There are perhaps other technologies in science that have yet to be realized by the chemist in the PET laboratory that could provide a similar or even a greater benefit. One only needs to be open to new ideas, and imaginative enough to apply them to the problems at hand.

  14. Production and application of synthetic precursors labeled with carbon-11 and fluorine-18

    International Nuclear Information System (INIS)

    It is evident from this chapter that there is enormous flexibility both in the selection of the nature of the radioisotope and ways to generate it, as well as in the selection of the labeling precursor to appropriately attach that radioisotope to some larger biomolecule of interest. The arsenal of radiolabeling precursors now available to the chemist is quite extensive, and without a doubt will continue to grow as chemists develop new ones. However, the upcoming years will perhaps reflect a greater effort in refining existing methods for preparing some of those precursors that are already available to us. For example, the use of solid-phase reactions to accomplish in a single step what would normally take several using conventional solvent-based reactions has already been shown to work in many occasions. The obvious advantage here is that processes become more amenable to system automation thus affording greater reliability in day-to-day operations. There are perhaps other technologies in science that have yet to be realized by the chemist in the PET laboratory that could provide a similar or even a greater benefit. One only needs to be open to new ideas, and imaginative enough to apply them to the problems at hand

  15. L-[METHYL-11C] Methionine Positron Emission Tomography for Target Delineation in Malignant Gliomas: Impact on Results of Carbon Ion Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To assess the importance of 11C-methionine (MET)-positron emission tomography (PET) for clinical target volume (CTV) delineation. Methods and Materials: This retrospective study analyzed 16 patients with malignant glioma (4 patients, anaplastic astrocytoma; 12 patients, glioblastoma multiforme) treated with surgery and carbon ion radiotherapy from April 2002 to Nov 2005. The MET-PET target volume was compared with gross tumor volume and CTV, defined by using computed tomography/magnetic resonance imaging (MRI). Correlations with treatment results were evaluated between positive and negative extended volumes (EVs) of the MET-PET target for CTV. Results: Mean volumes of the MET-PET targets, CTV1 (defined by means of high-intensity volume on T2-weighted MRI), and CTV2 (defined by means of contrast-enhancement volume on T1-weighted MRI) were 6.35, 264.7, and 117.7 cm3, respectively. Mean EVs of MET-PET targets for CTV1 and CTV2 were 0.6 and 2.2 cm3, respectively. The MET-PET target volumes were included in CTV1 and CTV2 in 13 (81.3%) and 11 patients (68.8%), respectively. Patients with a negative EV for CTV1 had significantly greater survival rate (p = 0.0069), regional control (p = 0.0047), and distant control time (p = 0.0267) than those with a positive EV. Distant control time also was better in patients with a negative EV for CTV2 than those with a positive EV (p = 0.0401). Conclusions: For patients with malignant gliomas, MET-PET has a possibility to be a predictor of outcome in carbon ion radiotherapy. Direct use of MET-PET fused to planning computed tomography will be useful and yield favorable results for the therapy

  16. Engineering of methionine chain elongation part of glucoraphanin pathway in E. coli.

    Science.gov (United States)

    Mirza, Nadia; Crocoll, Christoph; Erik Olsen, Carl; Ann Halkier, Barbara

    2016-05-01

    The methionine-derived glucosinolate glucoraphanin is associated with the health-promoting properties of broccoli. This has developed a strong interest in producing this compound in high amounts from a microbial source. Glucoraphanin synthesis starts with a five-gene chain elongation pathway that converts methionine to dihomo-methionine, which is subsequently converted to glucoraphanin by the seven-gene glucosinolate core structure pathway. As dihomo-methionine is the precursor amino acid for glucoraphanin production, a first challenge is to establish an expression system for production of dihomo-methionine. In planta, the methionine chain elongation enzymes are physically separated within the cell with the first enzyme in the cytosol while the rest are located in the chloroplast. A de-compartmentalization approach was applied to produce dihomo-methionine by expression of the respective plant genes in Escherichia coli cytosol. Introduction of two plasmids encoding the methionine chain elongation pathway into E. coli resulted in production of 25mgL(-1) of dihomo-methionine. In addition to chain-elongated methionine products, side-products from chain elongation of leucine were produced. Methionine supplementation enhanced dihomo-methionine production to 57mgL(-1), while keeping a steady level of the chain-elongated leucine products. Engineering of the de-compartmentalized pathway of dihomo-methionine in E. coli cytosol provides an important first step for microbial production of the health-promoting glucoraphanin. PMID:26410451

  17. Synthesis of [11C]interleukin 8 using a cell-free translation system and L-[11C]methionine

    International Nuclear Information System (INIS)

    Positron emission tomography (PET), which requires a compound labeled with a positron emitter radioisotope as an imaging probe, is one of the most useful and valuable imaging modalities in molecular imaging. It has several advantages over other imaging modalities, particularly in sensitive and quantitative investigations of molecular functions and processes in vivo. Recent advances in biopharmaceuticals development have increased interest in practical methods for proteins and peptides labeling with positron emitter radioisotope for PET molecular imaging. Here, we propose a novel approach for preparing positron emitter-labeled proteins and peptides based on biochemical synthesis using a reconstituted cell-free translation system. In this study, [11C]interleukin 8 (IL-8; MW 9.2 kDa) was successfully synthesized by the cell-free system in combination with L-[11C]methionine. The in vitro biochemical reaction proceeded smoothly and gave maximum radioactivity of [11C]IL-8 at 20 min with a radiochemical yield of 63%. Purification of [11C]IL-8 was achieved by conventional cation exchange and ultrafiltration methods, resulting in enough amount of radioactivity with excellent radiochemical purity (>95%) for small-animal imaging. This study clearly demonstrates that cell-free protein production system combined with positron emitter-labeled amino acid holds great promise as a novel approach to prepare radiolabeled proteins and peptides for PET imaging.

  18. Synthesis and biological evaluation of [{sup 11}C]talopram and [{sup 11}C]talsupram: candidate PET ligands for the norepinephrine transporter

    Energy Technology Data Exchange (ETDEWEB)

    McConathy, Jonathan; Owens, Michael J.; Kilts, Clinton D.; Malveaux, Eugene J.; Camp, Vernon M.; Votaw, John R.; Nemeroff, Charles B.; Goodman, Mark M. E-mail: mgoodma@emory.edu

    2004-08-01

    PET and SPECT ligands for the norepinephrine transporter (NET) will be important tools for studying the physiology, pathophysiology and pharmacology of the CNS noradrenergic system in vivo. A series of candidate NET ligands were synthesized and characterized in terms of their affinity for human monoamine transporters. The two most promising compounds, talopram and talsupram, were radiolabeled with carbon-11 and evaluated through biodistribution studies in rats and PET imaging studies in a rhesus monkey. Although both compounds displayed high affinity and selectivity for the human NET in vitro, these compounds did not enter the CNS in adequate amounts to be used in PET imaging studies.

  19. Maternal obesity disrupts the methionine cycle in baboon pregnancy.

    Science.gov (United States)

    Nathanielsz, Peter W; Yan, Jian; Green, Ralph; Nijland, Mark; Miller, Joshua W; Wu, Guoyao; McDonald, Thomas J; Caudill, Marie A

    2015-11-01

    Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized that maternal obesity would dysregulate the maternal and fetal methionine cycle. To test this hypothesis, we developed a nulliparous baboon obesity model fed a high fat, high energy diet (HF-HED) prior to and during gestation, and examined methionine cycle biomarkers (e.g., circulating concentrations of homocysteine, methionine, choline, betaine, key amino acids, folate, and vitamin B-12). Animals were group housed allowing full physical activity and social interaction. Maternal prepregnancy percent body fat was 5% in controls and 19% in HF-HED mothers, while fetal weight was 16% lower in offspring of HF-HED mothers at term. Maternal and fetal homocysteine were higher, while maternal and fetal vitamin B-12 and betaine were lower in the HF-HED group. Elevations in circulating maternal folate were evident in the HF-HED group indicating impaired folate metabolism (methyl-trap) as a consequence of maternal vitamin B-12 depletion. Finally, fetal methionine, glycine, serine, and taurine were lower in the HF-HED fetuses. These data show that maternal obesity disturbs the methionine cycle in primate pregnancy, providing a mechanism for the epigenetic changes observed among obese pregnant women and suggesting diagnostic and therapeutic opportunities in human pregnancies complicated by obesity. PMID:26537341

  20. Traumatic brain injury alters methionine metabolism: implications for pathophysiology

    Directory of Open Access Journals (Sweden)

    Pramod K Dash

    2016-04-01

    Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

  1. Separation Of Methionine Enantiomers By Using Teicoplanin And Cyclofructan Columns

    Directory of Open Access Journals (Sweden)

    Hroboňová Katarína

    2015-06-01

    Full Text Available Methionine is a naturally occurring amino acid. Its enantiomeric separation by using high performance liquid chromatography on various types of chiral stationary phases was studied. The effect of mobile phase composition on enantioselectivity and retention was considered. The separation of the enantiomers was attained in different separation modes – reversed phase mode for the macrocyclic antibiotic chiral stationary phases (teicoplanin, teicoplanin aglycone, normal phase and polar organic phase modes for the isopropyl carbamate cyclofructan 6 chiral stationary phase. It was shown that the hydrogen bonding, dipole interactions, steric effects between methionine molecules and stationary phases play an important role in the separation of enantiomers.

  2. Efficacy of C-11 L-methionine positron emission tomography and intraoperative methylene blue staining for localization of parathyroid glands in primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hiromasa; Takahashi, Masato; Taguchi, Kazunori; Takada, Naoyuki; Nakada, Kunihiro; Sasaki, Fumiaki; Todo, Satoru [Hokkaido Univ., Sapporo (Japan). School of Medicine

    2002-12-01

    For localization of parathyroid glands in primary hyperparathyroidism we carried out C-11 L-methionine positron emission tomography (Met-PET) in 10 patients (one with hyperplasia and 9 with adenoma) and intraoperative methylene blue staining in 20 patients (one with hyperplasia and 19 with adenoma) and compared the predictive value with that of US and {sup 99m}Tc-sestamibi scintigraphy (MIBI). Methylene blue was administrated at a calculated dose of 5 mg/kg body weight intravenously for 1 h before surgery. The accuracy of identification of pathological parathyroid glands with Met-PET, US and MIBI was 90%, 80% and 70% respectively. Met-PET was more sensitive than US and MIBI and could identify smaller parathyroid glands, particularly in cases with lower serum calcium levels. Met-PET imaging was not affected even in 2 reoperative cases. Intraoperative methylene blue staining of parathyroid glands was successful in 19 patients without major side effects. Met-PET was the most effective method for preoperative imaging of parathyroid glands. Intraoperative methylene blue staining was a safe and effective method and able to facilitate dissection of pathological glands during surgery. (author)

  3. PET / MRI vs. PET / CT. Indications Oncology

    International Nuclear Information System (INIS)

    Hybrid techniques in Nuclear Medicine is currently a field in full development for diagnosis and treatment of various medical conditions. With the recent advent of PET / MRI much it speculated about whether or not it is superior to PET / CT especially in oncology. The Conference seeks to clarify this situation by dealing issues such as: State of the art technology PET / MRI; Indications Oncology; Some clinical cases. It concludes by explaining the oncological indications of both the real and current situation of the PET / MRI. (author)

  4. PET/CT imaging in different types of lung cancer: An overview

    International Nuclear Information System (INIS)

    Lung cancer (LC) still represents one of the most common tumours in both women and men. PET/CT is a whole-body non-invasive imaging procedure that has been increasingly used for the assessment of LC patients. In particular, PET/CT added value to CT is mainly related to a more accurate staging of nodal and metastatic sites and to the evaluation of the response to therapy. Although the most common PET tracer for LC evaluation is 18F-FDG, new tracers have been proposed for the evaluation of lung neuroendocrine tumours (68Ga-DOTA-peptides, 18F-DOPA) and for the assessment of central nervous system metastasis (11C-methionine). This review focuses on the main clinical applications and accuracy of PET/CT for the detection of non-small cells lung cancer (NSCLC), broncho-alveolar carcinoma (BAC), small cells lung cancer (SCLC), lung neuroendocrine tumours (NET) and solitary pulmonary nodules (SPN).

  5. Synthesis and carbon-11 labeling of (R)- and (S)-thionisoxetine, norepinephrine reuptake inhibitors, potential radioligands for positron emission tomography

    International Nuclear Information System (INIS)

    Standards and des-methyl precursors of (R)- and (S)-thionisoxetine, potent and selective norepinephrine reuptake inhibitors, were synthesized and radiolabeled with carbon-11. Both enantiomers of the N-methyl-3-(2-thiomethylphenoxy)-3-phenylpropanamine and the 3-(2-thiomethylphenoxy)-3-phenylpropylamine were obtained via multi-step syntheses, while the radiosyntheses were carried out using [11C]CH3I. The radiochemical yields were 26%, decay corrected and the specific radioactivity ranging from 2 to 3 Ci/μmol. The HPLC analyses were performed using a chiral column: during the radiolabeling, no racemization occurred and the isomers were synthesized with high enantiomeric purity

  6. Synthesis of suicide inhibitors of monoamine oxidase: carbon-11 labeled clorgyline, L-deprenyl and D-deprenyl

    International Nuclear Information System (INIS)

    The suicide inhibitors of monoamine oxidase type A and B, clorgyline and L-deprenyl have been labeled with carbon-11 by [11C]methylation of the norbases with [11C]H3I. The less active enantiomer of deprenyl (D-deprenyl) was also labeled using this procedure. The synthesis time was 35 minutes, the radiochemical yield was 25-40% and the specific activity was 0.8-2.0 Ci/μmol (calculated to EOB). Procedures for synthesis of the precursor norbases as well as the synthesis of unlabeled clorgyline, L-deprenyl and D-deprenyl are given. (author)

  7. Does the Naked Neck Meat Type Chicken Yield Lower Methionine Requirement Data?

    OpenAIRE

    Khan, Daulat R.; Christian Wecke; Frank Liebert

    2015-01-01

    Simple Summary It was hypothesized that naked neck chickens could have a lower methionine requirement according to their reduced feather coverage. The hypothesis was examined by nitrogen balance studies and non-linear model application for estimating methionine requirement data of naked neck chickens. It was concluded that naked neck birds do not require less methionine than normally-feathered birds. Abstract Methionine (Met) requirement studies with homozygous (Na/Na) and heterozygous (Na/na...

  8. Modulation of potassium channel function by methionine oxidation and reduction

    OpenAIRE

    Ciorba, Matthew A; Heinemann, Stefan H.; Weissbach, Herbert; Brot, Nathan; Hoshi, Toshinori

    1997-01-01

    Oxidation of amino acid residues in proteins can be caused by a variety of oxidizing agents normally produced by cells. The oxidation of methionine in proteins to methionine sulfoxide is implicated in aging as well as in pathological conditions, and it is a reversible reaction mediated by a ubiquitous enzyme, peptide methionine sulfoxide reductase. The reversibility of methionine oxidation suggests that it could act as a cellular regulatory mechanism although no such in vivo activity has been...

  9. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  10. Clinical PET application

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang-Moo; Hong, S. W.; Choi, C. W.; Yang, S. D.; Choi, J. S.; Kweon, O. J. et al. [Korea Cancer Center Hospital, Seoul (Korea)

    2000-12-01

    PET gives various metabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 1,327 cases of PET images were obtained, which resulted total income of 829,770,000won. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18} in a day. Manpower should be added for the second PET operation and RI production. 10 figs., 4 tabs. (Author)

  11. Determination of the specific activities of methionine sulfoxide reductase A and B by capillary electrophoresis

    Science.gov (United States)

    A capillary electrophoresis (CE) method for the determination of methionine sulfoxide reductase A and methionine sulfoxide reductase B activities in mouse liver is described. The method is based on detection of the 4-(dimethylamino)azobenzene-4’-sulfonyl derivative of L-methionine (dabsyl Met), the ...

  12. Technical note: Methionine, a precursor of methane in living plants

    Directory of Open Access Journals (Sweden)

    K. Lenhart

    2014-11-01

    Full Text Available When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued, not only about their contribution to the global methane budget, but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds identified. We made use of stable isotope techniques to verify in vivo formation of methane and, in order to identify the carbon precursor, 13C-positionally labelled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labelled methionine clearly identified the sulphur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia. Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

  13. 21 CFR 172.372 - N-Acetyl-L-methionine.

    Science.gov (United States)

    2010-04-01

    ... protein efficiency ratio (PER) of protein in the finished ready-to-eat food equivalent to casein as... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... source of L-methionine to improve significantly the biological quality of the total protein in a...

  14. Report on compounds labelled with nitrogen-13 or carbon-11 used in cancer metabolic studies with quantitative two-dimensional scanning and pet tomography

    International Nuclear Information System (INIS)

    The use of compounds labelled with radionuclides of the elements commonly involved in metabolic processes (oxygen, carbon, nitrogen) is becoming important in the non-invasive study of organ and tumour function. The application of compounds labelled with 13N and 11C to the study of amino-acid metabolism and changes in vasculature following chemotherapy and radiation therapy is described. In particular, 13N-labelled L-glutamate has been found to be useful in visualizing a number of human tumours including osteogenic sarcoma, rhabdomyosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma, pineal gland tumours, primitive neuroectodermal tumours, medulloblastoma and several other solid tumours. In patients with bone tumours, changes in 13N-L-glutamate scans during chemotherapy were found to correlate with changes in other clinical parameters, such as serum alkaline phosphatase, histology and 99Tcsup(m)-bone scans, thus indicating that labelled L-glutamate is potentially useful in evaluating the response of solid tumours to chemotherapy. Scans of patients and volunteers using 13N-L-glutamate and 13N-L-valine indicate that the L-amino acids may be useful in studies of metabolic processes in the liver, myocardium and pancreas. Red blood cells, labelled with 11C-carbon monoxide via inhalation of the radioactive gas, have been used to assess changes in tumour vascularity following radiation therapy. Alpha-aminoisobutyric acid labelled with 11C has been synthesized and its distribution in normal and tumour-bearing dogs has been studied. (author)

  15. PET in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, Stefan (ed.) [HELIOS Klinikum Berlin-Buch, Berlin (Germany). Klinik fuer Nuklearmedizin

    2008-07-01

    In the management of oncologic diseases, modern imaging modalities contribute heavily to the decision of which form of treatment - local or systemic, surgical or interdisciplinary - will be most efficient. The addition of functional image information to conventional staging procedures helps improve the diagnostic pathway. The information needed for therapeutic management and for follow-up can be provided by correlative imaging such as positron emission tomography (PET) and computed tomography (CT) or PET/CT. This book is a comprehensive compilation of the accumulated knowledge on PET and PET/CT in oncology, covering the entire spectrum from solidly documented indications, such as staging and monitoring of lung and colorectal cancer, to the application of PET/CT in head and neck surgery, gynecology, radiation therapy, urology, pediatrics etc. It is aimed at nuclear medicine and radiology specialists as well as physicians interested in the possibilities and limitations of PET and PET/CT in oncology. (orig.)

  16. Efficacy of DL-methionine hydroxy analogue-free acid in comparison to DL-methionine in growing male white Pekin ducks.

    Science.gov (United States)

    Kluge, H; Gessner, D K; Herzog, E; Eder, K

    2016-03-01

    The present study was performed to assess the bioefficacy of DL-methionine hydroxy analogue-free acid (MHA) in comparison to DL-methionine (DLM) as sources of methionine for growing male white Pekin ducks in the first 3 wk of life. For this aim, 580 1-day-old male ducks were allocated into 12 treatment groups and received a basal diet that contained 0.29% of methionine, 0.34% of cysteine and 0.63% of total sulphur containing amino acids or the same diet supplemented with either DLM or MHA in amounts to supply 0.05, 0.10, 0.15, 0.20, and 0.25% of methionine equivalents. Ducks fed the control diet without methionine supplement had the lowest final body weights, daily body weight gains and feed intake among all groups. Supplementation of methionine improved final body weights and daily body weight gains in a dose dependent-manner. There was, however, no significant effect of the source of methionine on all of the performance responses. Evaluation of the data of daily body weight gains with an exponential model of regression revealed a nearly identical efficacy (slope of the curves) of both compounds for growth (DLM = 100%, MHA = 101%). According to the exponential model of regression, 95% of the maximum values of daily body weight gain were reached at methionine supplementary levels of 0.080% and 0.079% for DLM and MHA, respectively. Overall, the present study indicates that MHA and DLM have a similar efficacy as sources of methionine for growing ducks. It is moreover shown that dietary methionine concentrations of 0.37% are required to reach 95% of the maximum of daily body weight gains in ducks during the first 3 wk of life. PMID:26706358

  17. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-[11C]dimethyltryptamine

    International Nuclear Information System (INIS)

    The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [11C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [11C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [11C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors. (orig.)

  18. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-(/sup 11/C)dimethyltryptamine

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, Kazuhiko; Ido, Tatsuo; Ishiwata, Kiichi; Takahashi, Toshihiro; Iwata, Ren; Hatazawa, Jun; Matsuzawa, Taiju

    1986-07-01

    The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. (/sup 11/C)DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of (/sup 11/C)DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of (/sup 11/C)DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.

  19. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-[11C]dimethyltryptamine.

    Science.gov (United States)

    Yanai, K; Ido, T; Ishiwata, K; Hatazawa, J; Takahashi, T; Iwata, R; Matsuzawa, T

    1986-01-01

    The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [11C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [11C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [11C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors. PMID:3489620

  20. Biodistribution of a positron-emitting suicide inactivator of monoamine oxidase, carbon-11 pargyline, in mice and a rabbit

    International Nuclear Information System (INIS)

    Carbon-11 (11C) pargyline, which is a suicide inactivator of Type B monoamine oxidase (MAO), was synthesized by the reaction of N-demethylpargyline with 11CH3l. Biodistribution was investigated in mice, and positron tomographic images of the heart and lung in a rabbit were obtained. The distribution of 11C after administration of [11C]pargyline was measured in several organs and blood at various time intervals. After 30 min its concentrations in the organs were constant. Subcellular distribution studies in the brain, lung, liver, and kidney showed that 59-70% of the 11C became acid-insoluble and 9-33% was present in the crude mitochondrial fraction at 60 min after injection. The uptakes of the 11C in each organ except for the kidney and spleen seemed to correlate with the in vitro enzymatic activity of Type B MAO. At high loading dose a nonspecific uptake was observed

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

    International Nuclear Information System (INIS)

    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)

  2. Structure of methionine γ-lyase from Clostridium sporogenes.

    Science.gov (United States)

    Revtovich, Svetlana; Anufrieva, Natalya; Morozova, Elena; Kulikova, Vitalia; Nikulin, Alexey; Demidkina, Tatyana

    2016-01-01

    Methionine γ-lyase (MGL) is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the γ-elimination reaction of L-methionine. The enzyme is a promising target for therapeutic intervention in some anaerobic pathogens and has attracted interest as a potential cancer treatment. The crystal structure of MGL from Clostridium sporogenes has been determined at 2.37 Å resolution. The fold of the protein is similar to those of homologous enzymes from Citrobacter freundii, Entamoeba histolytica, Pseudomonas putida and Trichomonas vaginalis. A comparison of these structures revealed differences in the conformation of two flexible regions of the N- and C-terminal domains involved in the active-site architecture. PMID:26750487

  3. Salmonella: Dry Pet Foods and Pet Treats (FAQ)

    Science.gov (United States)

    ... Guides Reports Salmonella: Dry Pet Foods and Pet Treats (FAQ) Originally posted August 9, 2010; Updated August ... as a result of the outbreak. “Natural” pet treats , such as pig ears and dehydrated/dried beef ...

  4. Maternal obesity disrupts the methionine cycle in baboon pregnancy

    OpenAIRE

    Nathanielsz, Peter W.; Yan, Jian; Green, Ralph; Nijland, Mark; Miller, Joshua W.; Wu, Guoyao; McDonald, Thomas J; Caudill, Marie A.

    2015-01-01

    Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized t...

  5. Separation Of Methionine Enantiomers By Using Teicoplanin And Cyclofructan Columns

    OpenAIRE

    Hroboňová Katarína; Deáková Zuzana; Moravčík Jakub; Lehotay Jozef; Armstrong Daniel W.; Lomenová Anna

    2015-01-01

    Methionine is a naturally occurring amino acid. Its enantiomeric separation by using high performance liquid chromatography on various types of chiral stationary phases was studied. The effect of mobile phase composition on enantioselectivity and retention was considered. The separation of the enantiomers was attained in different separation modes – reversed phase mode for the macrocyclic antibiotic chiral stationary phases (teicoplanin, teicoplanin aglycone), normal phase and polar organic p...

  6. Comparative genomics of transcriptional regulation of methionine metabolism in Proteobacteria.

    Directory of Open Access Journals (Sweden)

    Semen A Leyn

    Full Text Available Methionine metabolism and uptake genes in Proteobacteria are controlled by a variety of RNA and DNA regulatory systems. We have applied comparative genomics to reconstruct regulons for three known transcription factors, MetJ, MetR, and SahR, and three known riboswitch motifs, SAH, SAM-SAH, and SAM_alpha, in ∼ 200 genomes from 22 taxonomic groups of Proteobacteria. We also identified two novel regulons: a SahR-like transcription factor SamR controlling various methionine biosynthesis genes in the Xanthomonadales group, and a potential RNA regulatory element with terminator-antiterminator mechanism controlling the metX or metZ genes in beta-proteobacteria. For each analyzed regulator we identified the core, taxon-specific and genome-specific regulon members. By analyzing the distribution of these regulators in bacterial genomes and by comparing their regulon contents we elucidated possible evolutionary scenarios for the regulation of the methionine metabolism genes in Proteobacteria.

  7. Comparative genomics of transcriptional regulation of methionine metabolism in Proteobacteria.

    Science.gov (United States)

    Leyn, Semen A; Suvorova, Inna A; Kholina, Tatiana D; Sherstneva, Sofia S; Novichkov, Pavel S; Gelfand, Mikhail S; Rodionov, Dmitry A

    2014-01-01

    Methionine metabolism and uptake genes in Proteobacteria are controlled by a variety of RNA and DNA regulatory systems. We have applied comparative genomics to reconstruct regulons for three known transcription factors, MetJ, MetR, and SahR, and three known riboswitch motifs, SAH, SAM-SAH, and SAM_alpha, in ∼ 200 genomes from 22 taxonomic groups of Proteobacteria. We also identified two novel regulons: a SahR-like transcription factor SamR controlling various methionine biosynthesis genes in the Xanthomonadales group, and a potential RNA regulatory element with terminator-antiterminator mechanism controlling the metX or metZ genes in beta-proteobacteria. For each analyzed regulator we identified the core, taxon-specific and genome-specific regulon members. By analyzing the distribution of these regulators in bacterial genomes and by comparing their regulon contents we elucidated possible evolutionary scenarios for the regulation of the methionine metabolism genes in Proteobacteria. PMID:25411846

  8. Potential for Development of an Escherichia coli—Based Biosensor for Assessing Bioavailable Methionine: A Review

    Directory of Open Access Journals (Sweden)

    Vesela I. Chalova

    2010-04-01

    Full Text Available Methionine is an essential amino acid for animals and is typically considered one of the first limiting amino acids in animal feed formulations. Methionine deficiency or excess in animal diets can lead to sub-optimal animal performance and increased environmental pollution, which necessitates its accurate quantification and proper dosage in animal rations. Animal bioassays are the current industry standard to quantify methionine bioavailability. However, animal-based assays are not only time consuming, but expensive and are becoming more scrutinized by governmental regulations. In addition, a variety of artifacts can hinder the variability and time efficacy of these assays. Microbiological assays, which are based on a microbial response to external supplementation of a particular nutrient such as methionine, appear to be attractive potential alternatives to the already established standards. They are rapid and inexpensive in vitro assays which are characterized with relatively accurate and consistent estimation of digestible methionine in feeds and feed ingredients. The current review discusses the potential to develop Escherichia coli-based microbial biosensors for methionine bioavailability quantification. Methionine biosynthesis and regulation pathways are overviewed in relation to genetic manipulation required for the generation of a respective methionine auxotroph that could be practical for a routine bioassay. A prospective utilization of Escherichia coli methionine biosensor would allow for inexpensive and rapid methionine quantification and ultimately enable timely assessment of nutritional profiles of feedstuffs.

  9. The Pediatric Methionine Requirement Should Incorporate Remethylation Potential and Transmethylation Demands.

    Science.gov (United States)

    Robinson, Jason L; Bertolo, Robert F

    2016-05-01

    The metabolic demand for methionine is great in neonates. Indeed, methionine is the only indispensable sulfur amino acid and is required not only for protein synthesis and growth but is also partitioned to a greater extent to transsulfuration for cysteine and taurine synthesis and to >50 transmethylation reactions that serve to methylate DNA and synthesize metabolites, including creatine and phosphatidylcholine. Therefore, the pediatric methionine requirement must accommodate the demands of rapid protein turnover as well as vast nonprotein demands. Because cysteine spares the methionine requirement, it is likely that the dietary provision of transmethylation products can also feasibly spare methionine. However, understanding the requirement of methionine is further complicated because demethylated methionine can be remethylated by the dietary methyl donors folate and betaine (derived from choline). Intakes of dietary methyl donors are highly variable, which is of particular concern for newborns. It has been demonstrated that many populations have enhanced requirements for these nutrients, and nutrient fortification may exacerbate this phenomenon by selecting phenotypes that increase methyl requirements. Moreover, higher transmethylation rates can limit methyl supply and affect other transmethylation reactions as well as protein synthesis. Therefore, careful investigations are needed to determine how remethylation and transmethylation contribute to the methionine requirement. The purpose of this review is to support our hypothesis that dietary methyl donors and consumers can drive methionine availability for protein synthesis and transmethylation reactions. We argue that nutritional strategies in neonates need to ensure that methionine is available to meet requirements for growth as well as for transmethylation products. PMID:27184279

  10. Effect of cysteine on methionine production by a regulatory mutant of Corynebacterium lilium

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Dharmendra; Subramanian, Kartik; Bisaria, Virendra S.; Sreekrishnan, T.R.; Gomes, James [Indian Inst. of Technology, Dept. of Biochemical Engineering and Biotechnology, New Delhi (India)

    2005-02-01

    The production of methionine by submerged fermentation using a mutant strain of Corynebacterium lilium was studied to determine suitable conditions for obtaining high productivity. The mutant strain resistant to the methionine analogues ethionine, norleucine, methionine sulfoxide and methionine methylsulfonium chloride produced 2.34 g l{sup -1} of methionine in minimal medium containing glucose as carbon source. The effect of cysteine on methionine production in a 15 l bioreactor was studied by supplementing cysteine intermittently during the course of fermentation. The addition of cysteine (0.75 g l{sup -1} h{sup -1}) every 2 h to the production medium increased the production of methionine to 3.39 g l{sup -1}. A metabolic flux analysis showed that during cysteine supplementation the ATP consumption reduced by 20%. It also showed that the increase in flux from phosphoenol pyruvate to oxaloacetate leads to higher methionine production. Results indicate that controlling the respiratory quotient close to 0.75 will produce the highest amount of methionine and that regulatory mutants also resistant to analogues of cysteine would be better methionine over producers. (Author)

  11. Radiosynthesis and in vivo evaluation of fluorinated huprine derivates as PET radiotracers of acetylcholinesterase

    International Nuclear Information System (INIS)

    Introduction: Developing positron emission tomography (PET) radiotracers for non-invasive study of the cholinergic system is crucial to the understanding of neurodegenerative diseases. Although several acetylcholinesterase (AChE) PET tracers radiolabeled with carbon-11 exist, no fluorinated radiotracer is currently used in clinical imaging studies. The purpose of the present study is to describe the first fluorinated PET radiotracer for this brain enzyme. Methods: Three structural analogs of huprine, a specific AChE inhibitor presenting high affinity towards AChE in vitro, were synthesized and labeled with fluorine-18 via a mesylate/fluoro-nucleophilic aliphatic substitution: ([18 F]-FHUa, [18 F]-FHUb and [18 F]-FHUc). Initial biological evaluation included in vitro autoradiography in rat with competition with an AChE inhibitor at different concentrations, and microPET-scan on anesthetized rats. In vivo PET studies in anesthetized cat focused on [18 F]-FHUa. Results and Conclusions: Although radiosynthesis of these huprine analogs was straightforward, they showed poor brain penetration potential, partially reversed after pharmacological inhibition of P-glycoprotein. These results indicated that current huprine analogs are not suitable for PET mapping of brain AChE receptors, but require physicochemical modulation in order to increase brain penetration

  12. Soluble methionine enhances accumulation of a 15 kDa zein, a methionine-rich storage protein, in transgenic alfalfa but not in transgenic tobacco plants.

    Science.gov (United States)

    Amira, Golan; Ifat, Matityahu; Tal, Avraham; Hana, Badani; Shmuel, Galili; Rachel, Amir

    2005-09-01

    With the general aim of elevating the content of the essential amino acid methionine in vegetative tissues of plants, alfalfa (Medicago sativa L.) and tobacco plants, as well as BY2 tobacco suspension cells, were transformed with a beta-zein::3HA gene under the 35S promoter of cauliflower mosaic virus encoding a rumen-stable methionine-rich storage protein of 15 kDa zein. To examine whether soluble methionine content limited the accumulation of the 15 kDa zein::3HA, methionine was first added to the growth medium of the different transgenic plants and the level of the alien protein was determined. Results demonstrated that the added methionine enhanced the accumulation of the 15 kDa zein::3HA in transgenic alfalfa and tobacco BY2 cells, but not in whole transgenic tobacco plants. Next, the endogenous levels of methionine were elevated in the transgenic tobacco and alfalfa plants by crossing them with plants expressing the Arabidopsis cystathionine gamma-synthase (AtCGS) having significantly higher levels of soluble methionine in their leaves. Compared with plants expressing only the 15 kDa zein::3HA, transgenic alfalfa co-expressing both alien genes showed significantly enhanced levels of this protein concurrently with a reduction in the soluble methionine content, thus implying that soluble methionine was incorporated into the 15 kDa zein::3HA. Similar phenomena also occurred in tobacco, but were considerably less pronounced. The results demonstrate that the accumulation of the 15 kDa zein::3HA is regulated in a species-specific manner and that soluble methionine plays a major role in the accumulation of the 15 kDa zein in some plant species but less so in others. PMID:16061510

  13. Clinical PET application

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Hong, Song W.; Choi, Chang W.; Yang, Seong Dae [Korea Cancer Center Hospital, Seoul (Korea)

    1997-12-01

    PET gives various methabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 250 cases of PET images were obtained, which resulted total income of 180,000,000 won. 50,000,000 won was deposited for the 1998 PET clinical research. Second year PET clinical research should be managed under unified project. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18}FDG in a day purchase of HPLC pump and {sup 68}Ga pin source which was delayed due to economic crisis, should be done early in 1998. (author). 2 figs., 3 tabs.

  14. Comparative studies of potential cancer biomarkers carbon-11 labeled MMP inhibitors (S)-2-(4'-[11C]methoxybiphenyl-4-sulfonylamino)-3-methylbutyric acid and N-hydroxy-(R)-2-[[(4'-[11C]methoxyphenyl)sulfonyl]benzylamino]-3 -methylbutanamide

    International Nuclear Information System (INIS)

    (S)-2-(4'-[11C]methoxybiphenyl-4-sulfonylamino)-3-methylbutyric acid ([11C]MSMA) and N-hydroxy-(R)-2-[[(4'-[11C]methoxyphenyl)sulfonyl]benzylamino]-3- methylbutanamide ([11C]CGS 25966), carbon-11 labeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarkers. [11C]MSMA was prepared by appropriate precursory droxybiphenyl-4-sulfonylamino)-3-methylbutyric acid tert-butyl ester, which was synthesized in eight steps from amino acid (L)-valine in 39.4% chemical yield. This precursor was labeled by [11C]methyl triflate through O-[11C]methylation method at the hydroxyl position of biphenol under basic conditions, followed by a quick acid hydrolysis and isolated by solid-phase extraction (SPE) purification to produce pure target compound [11C]MSMA in 35-55% radiochemical yield, based on 11CO2, decay corrected to end of bombardment (EOB), and 20-25 min synthesis time. [11C]CGS 25966 was prepared in our previous work starting from amino acid (D)-valine. The biodistribution of [11C]MSMA and [11C]CGS 25966 were determined at 45 min post iv injection in breast cancer animal models MCF-7's transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [11C]MSMA and [11C]CGS 25966 in these tumors were 0.95 and 0.42%dose/g in MCF-7's transfected with IL-1α implanted mice, 0.98 and 1.53%dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.21 and 1.09 (T/M, MCF-7's), 0.99 and 0.84 (T/B, MCF-7's), 1.38 and 1.27 (T/M, MDA-MB-435), 1.27 and 1.95 (T/B, MDA-MB-435), respectively. The micro-PET images of [11C]MSMA and [11C]CGS 25966 in both breast cancer athymic mice were acquired for 15 min from a MCF-7's transfected with IL-1α and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (11C]MSMA and [11C]CGS 25966

  15. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS

    International Nuclear Information System (INIS)

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation

  16. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS.

    Energy Technology Data Exchange (ETDEWEB)

    Alexoff, D.L.

    2001-09-21

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation.

  17. Potential for Development of an Escherichia coli—Based Biosensor for Assessing Bioavailable Methionine: A Review

    OpenAIRE

    Vesela I. Chalova; Froelich, Clifford A.; Ricke, Steven C.

    2010-01-01

    Methionine is an essential amino acid for animals and is typically considered one of the first limiting amino acids in animal feed formulations. Methionine deficiency or excess in animal diets can lead to sub-optimal animal performance and increased environmental pollution, which necessitates its accurate quantification and proper dosage in animal rations. Animal bioassays are the current industry standard to quantify methionine bioavailability. However, animal-based assays are not only time ...

  18. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lerberg; Afzelius, Pia; Bender, Dirk;

    2015-01-01

    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11......)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a...... sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis...

  19. Effect of gamma irradiation on methionine and tryptophan content in soya protein products

    International Nuclear Information System (INIS)

    Effect of gamma irradiation on the content of methionine and tryptophan in soya protein products were investigated. Irradiation with doses of 1, 3 and 5 kGy caused significant (p = 0.05) decrease of methionine contents. Parallel with the decrease in methionine also the relative quality of proteins is lowered. Tryptophan content were significantly reduced (p = 0.05) at irradiation doses of 3 and 5 kGy. The relative decrease of methionine and tryptophan contents are significantly correlated (p = 0.05) with relative increase in amount of products by the irradiation induced oxidation of lipids; correlation coefficients were 0.576 and 0.715

  20. Higher endogenous methionine in transgenic Arabidopsis seeds affects the composition of storage proteins and lipids.

    Science.gov (United States)

    Cohen, Hagai; Pajak, Agnieszka; Pandurangan, Sudhakar; Amir, Rachel; Marsolais, Frédéric

    2016-06-01

    Previous in vitro studies demonstrate that exogenous application of the sulfur-containing amino acid methionine into cultured soybean cotyledons and seedlings reduces the level of methionine-poor storage proteins and elevates those that are methionine-rich. However, the effect of higher endogenous methionine in seeds on the composition of storage products in vivo is not studied yet. We have recently produced transgenic Arabidopsis seeds having significantly higher levels of methionine. In the present work we used these seeds as a model system and profiled them for changes in the abundances of 12S-globulins and 2S-albumins, the two major groups of storage proteins, using 2D-gels and MALDI-MS detection. The findings suggest that higher methionine affects from a certain threshold the accumulation of several subunits of 12S-globulins and 2S-albumins, regardless of their methionine contents, resulting in higher total protein contents. The mRNA abundances of most of the genes encoding these proteins were either correlated or not correlated with the abundances of these proteins, implying that methionine may regulate storage proteins at both transcriptional and post-transcriptional levels. The elevations in total protein contents resulted in reduction of total lipids and altered the fatty acid composition. Altogether, the data provide new insights into the regulatory roles of elevated methionine levels on seed composition. PMID:26888094

  1. HIV and pet ownership.

    Science.gov (United States)

    Downing, D

    1995-01-01

    The Centers for Disease Control and Prevention (CDC) states that there is no evidence that dogs, cats or non-primate animals can contract the human immunodeficiency virus (HIV) or transmit it to human beings. When the immune system is suppressed through disease, age, or medical treatments, a person becomes more vulnerable to infections. Pets Are Wonderful Support (PAWS) has developed guidelines for having pets. Proper pet selection, proper pet care and good personal hygiene of the owner can eliminate almost any possible risk a pet poses. New pets pose more of a health risk because health history and vaccination records are usually not known. Adult pets are often safer, and are less likely to be involved in playful activities that include biting and scratching. There is a slim chance of contracting toxoplasmosis from cats, but certain precautions can minimize risk. Annual veterinarian examinations are recommended to keep vaccinations current. The CDC does not recommend keeping a cat with feline leukemia virus or feline immunodeficiency virus since these diseases can make the cat more susceptible to other illnesses which can be passed on to a person with a compromised immune system. Turtles and birds are not recommended since they may harbor diseases. Several services are available to pet owners and are listed in the article. PMID:11362398

  2. My Pet Rock

    Science.gov (United States)

    Lark, Adam; Kramp, Robyne; Nurnberger-Haag, Julie

    2008-01-01

    Many teachers and students have experienced the classic pet rock experiment in conjunction with a geology unit. A teacher has students bring in a "pet" rock found outside of school, and the students run geologic tests on the rock. The tests include determining relative hardness using Mohs scale, checking for magnetization, and assessing luster.…

  3. Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1-13C]methionine

    International Nuclear Information System (INIS)

    The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3-methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L-cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine

  4. Clinical PET: changing the practice of oncology

    International Nuclear Information System (INIS)

    disease, we have been able to demonstrate that PET has a high and appropriate impact on management. Our group have recently published data on the clinical impact of PET in specific diseases including the staging of NSCLC, the restaging of NSCLC, the staging of cervical cancer, the restaging of colorectal cancer, the diagnosis of solitary pulmonary nodules, evaluation of lymphoma and malignant melanoma. The uptake of FDG in inflammatory conditions, leading to false positive results, is regarded as one of the major limitations of this tracer in oncological settings. In an attempt to address this limitation agents that look at biological processes more specific to cancers than is glycolytic metabolism, have been evaluated. These include amino acid analogues that trace protein synthesis, thymidine analogues that evaluate cellular proliferation, and markers of cellular sterol metabolism. An additional feature of cancers is the presence of hypoxia. PET tracers such as F-18 fluoromisonidazole have been shown to be taken up in a high percentage of some tumours that clinical and experimental evidence suggests are likely to be hypoxic and because of this, more resistant to conventional therapies. Additional potential limitation of FDG is the potential for an increase in uptake during the process of apoptosis, an energy requiring process, that may limit the utility of early scanning to determine therapeutic response. The so-called 'metabolic flare' has been described as actually being predictive of therapeutic response in breast cancer patients treated by hormone manipulation. Due to issues related to synthesis times and providing adequate tracer amounts for several studies at least, we have focussed on fluorinated PET tracers rather than shorter-lived tracers using carbon-11. Currently the Peter MacCallum Cancer Institute Centre for Molecular Imaging has active clinical research trials using the cellular proliferative tracer, F-18 fluorothymidine (FLT), and the hypoxia markers F-18

  5. PET and PET/CT for imaging of prostate cancer

    International Nuclear Information System (INIS)

    This review article provides an overview of the current literature data regarding the value of PET and PET/CT for imaging of prostate cancer. Most widely used PET tracers for prostate cancer imaging are 11C-acetate and 11C- or 18F-labeled choline. Available literature data on the performance of PET and PET/CT in the detection of the primary malignancy as well as local or distant metastases are presented and discussed. In addition, our own preliminary results regarding the diagnostic efficacy of 11C-choline PET and PET/CT in 43 patients with suspected prostate cancer are provided. The prevalence of prostate cancer in this patient sample was 55.8%. PET and PET/CT showed a sensitivity of 88% with a specificity of 63% in the detection of the primary prostate cancer. The sensitivity in the detection of metastatic spread was 77% and no false-positives were found. The possible value and limitations of combined PET/CT systems when compared to stand alone PET scanners are discussed. PET and PET/CT is at present the single imaging modality providing functional information not only regarding the primary malignancy but also its metastases. This unique feature distinguishes PET from MRI complemented with magnetic resonance spectroscopy - a competing procedure. Our own results as well as the still limited literature data suggest, that PET and PET/CT may prove to be useful methods for imaging of prostate cancer. (orig.)

  6. Usage of Recycled Pet

    Directory of Open Access Journals (Sweden)

    A. Ebru Tayyar

    2010-01-01

    Full Text Available The increasing industrialization, urbanization and the technological development have caused to increase depletion of the natural resources and environmental pollution's problem. Especially, for the countries which have not enough space recycling of the waste eliminating waste on regular basis or decreasing the amount and volume of waste have provided the important advantages. There are lots of studies and projects to develop both protect resources and prevent environmental pollution. PET bottles are commonly used in beverage industry and can be reused after physical and chemical recycling processes. Usage areas of recycled PET have been developed rapidly. Although recycled PET is used in plastic industry, composite industry also provides usage alternatives of recycled PET. Textile is a suitable sector for recycling of some plastics made of polymers too. In this study, the recycling technologies and applications of waste PET bottles have been investigated and scientific works in this area have been summarized.

  7. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    DEFF Research Database (Denmark)

    Afzelius, Pia Maria Tullia; Nielsen, Ole L; Alstrup, Aage Ko;

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for......-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with...

  8. Novel tracer for radiation treatment planning; Welche neuen PET-Tracer braucht die Strahlentherapie?

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, S.; Krause, B.J. [Rostock Univ. (Germany). Klinik fuer Nuklearmedizin; Herrmann, K.; Gaertner, F.; Souvatzoglou, M. [Technische Univ. Muenchen (Germany). Klinik fuer Nuklearmedizin; Klaesner, B. [Klinikum Bogenhausen, Muenchen (Germany). Inst. fuer Radiologie und Nuklearmedizin

    2011-07-15

    PET and PET/CT with innovative tracers gain increasing importance in diagnosis and therapy management, and radiation treatment planning in radio-oncology besides the widely established FDG. The introduction of [{sup 18}F]Fluorothymidine ([{sup 18}F]FLT) as marker of proliferation, [{sup 18}F]Fluoromisonidazole ([{sup 18}F]FMISO) and [{sup 18}F]Fluoroazomycin-Arabinoside ([{sup 18}F]FAZA) as tracer of hypoxia, [{sup 18}F]Fluoroethyltyrosine ([{sup 18}F]FET) and [{sup 11}C]Methionine for brain tumour imaging, [{sup 68}Ga]DOTATOC for somatostatin receptor imaging, [{sup 18}F]FDOPA for dopamine synthesis and radioactively labeled choline derivatives for imaging phospholipid metabolism have opened novel approaches to tumour imaging. Some of these tracers have already been implemented into radio-oncology: Amino acid PET and PET/CT have the potential to optimise radiation treatment planning of brain tumours through accurate delineation of tumour tissue from normal tissue, necrosis and edema. Hypoxia represents a major therapeutic problem in radiation therapy. Hypoxia imaging is very attractive as it may allow to increase the dose in hypoxic tumours potentially allowing for a better tumour control. Advances in hybrid imaging, i.e. the introduction of MR/PET, may also have an impact in radio-oncology through synergies related to the combination of molecular signals of PET and a high soft tissue contrast of MRI as well as functional MRI capabilities. (orig.)

  9. Insights into the reactivation of cobalamin-dependent methionine synthase

    Energy Technology Data Exchange (ETDEWEB)

    Koutmos, Markos; Datta, Supratim; Pattridge, Katherine A.; Smith, Janet L.; Matthews, Rowena G.; (Michigan)

    2009-12-10

    Cobalamin-dependent methionine synthase (MetH) is a modular protein that catalyzes the transfer of a methyl group from methyltetrahydrofolate to homocysteine to produce methionine and tetrahydrofolate. The cobalamin cofactor, which serves as both acceptor and donor of the methyl group, is oxidized once every {approx}2,000 catalytic cycles and must be reactivated by the uptake of an electron from reduced flavodoxin and a methyl group from S-adenosyl-L-methionine (AdoMet). Previous structures of a C-terminal fragment of MetH (MetH{sup CT}) revealed a reactivation conformation that juxtaposes the cobalamin- and AdoMet-binding domains. Here we describe 2 structures of a disulfide stabilized MetH{sup CT} ({sub s-s}MetH{sup CT}) that offer further insight into the reactivation of MetH. The structure of {sub s-s}MetH{sup CT} with cob(II)alamin and S-adenosyl-L-homocysteine represents the enzyme in the reactivation step preceding electron transfer from flavodoxin. The structure supports earlier suggestions that the enzyme acts to lower the reduction potential of the Co(II)/Co(I) couple by elongating the bond between the cobalt and its upper axial water ligand, effectively making the cobalt 4-coordinate, and illuminates the role of Tyr-1139 in the stabilization of this 4-coordinate state. The structure of {sub s-s}MetH{sub CT} with aquocobalamin may represent a transient state at the end of reactivation as the newly remethylated 5-coordinate methylcobalamin returns to the 6-coordinate state, triggering the rearrangement to a catalytic conformation.

  10. The effects of enhanced methionine synthesis on amino acid and anthocyanin content of potato tubers

    Directory of Open Access Journals (Sweden)

    Bánfalvi Zsófia

    2008-06-01

    Full Text Available Abstract Background Potato is a staple food in the diet of the world's population and also being used as animal feed. Compared to other crops, however, potato tubers are relatively poor in the essential amino acid, methionine. Our aim was to increase the methionine content of tubers by co-expressing a gene involved in methionine synthesis with a gene encoding a methionine-rich storage protein in potato plants. Results In higher plants, cystathionine γ-synthase (CgS is the first enzyme specific to methionine biosynthesis. We attempted to increase the methionine content of tubers by expressing the deleted form of the Arabidopsis CgS (CgSΔ90, which is not regulated by methionine, in potato plants. To increase the incorporation of free methionine into a storage protein the CgSΔ90 was co-transformed with the methionine-rich 15-kD β-zein. Results demonstrated a 2- to 6-fold increase in the free methionine content and in the methionine content of the zein-containing protein fraction of the transgenic tubers. In addition, in line with higher methionine content, the amounts of soluble isoleucine and serine were also increased. However, all of the lines with high level of CgSΔ90 expression were phenotypically abnormal showing severe growth retardation, changes in leaf architecture and 40- to 60% reduction in tuber yield. Furthermore, the colour of the transgenic tubers was altered due to the reduced amounts of anthocyanin pigments. The mRNA levels of phenylalanine ammonia-lyase (PAL, the enzyme catalysing the first step of anthocyanin synthesis, were decreased. Conclusion Ectopic expression of CgSΔ90 increases the methionine content of tubers, however, results in phenotypic aberrations in potato. Co-expression of the 15-kD β-zein with CgSΔ90 results in elevation of protein-bound methionine content of tubers, but can not overcome the phenotypical changes caused by CgSΔ90 and can not significantly improve the nutritional value of tubers. The level

  11. Methionine aminopeptidase gene of Escherichia coli is essential for cell growth.

    OpenAIRE

    Chang, S. Y.; McGary, E C; Chang, S.

    1989-01-01

    We localized the methionine aminopeptidase (map) gene on the Escherichia coli chromosome next to the rpsB gene at min 4. Genetically modified strains with the chromosomal map gene under lac promoter control grew only in the presence of the lac operon inducer isopropyl-beta-thiogalactoside. Thus, methionine aminopeptidase is essential for cell growth.

  12. FDG-PET and MET-PET for differentiation between benign lesions and lung cancer in pneumoconiosis

    International Nuclear Information System (INIS)

    We retrospectively assessed the usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) and methionine (MET)-PET for the differentiation between benign lesions and lung cancer in patients with pneumoconiosis. A total of 54 patients with pneumoconiosis underwent both wholebody MET-PET and FDG-PET on the same day. Of the 54 patients, 50 were former coal miners. These patients were divided into three groups. The first was lung cancer group, which consisted of 12 patients with pneumoconiosis (4 with squamous cell carcinoma, 6 with adenocarcinoma, 1 with small cell carcinoma, 1 with large cell carcinoma). The second was benign lesion group, which consisted of 21 patients with pneumoconiosis. These subject had no evidence of lung cancer, which was confirmed on the basis of a long term follow-up to date. The third was control group, which consisted of 21 patients with pneumoconiosis. In the pneumoconiotic nodules, significant correlation between nodule size and standardized uptake value (SUV)max of the two PET tracers were observed, and the SUVmax of MET was lower than that of FDG. The SUVmax of benign lesions were not different from that of pneumoconiotic nodules. In FDG and MET-PET study, the SUVmax of lung cancer measuring more than 2 cm and less than 3 cm in diameter were significantly higher than that of pneumoconiotic nodules. In the 3 cases of bronchiolo-alveolar cell carcinoma (BAC), no abnormal accumulation was observed by either FDG or MET. A cut-off value of SUVmax of FDG-PET which we determined for differentiating lung cancer from pneumoconiotic nodules is 4 in nodules with diameter less than 3 cm, 6 with diameter more than 3 cm and less than 4 cm, and 9 with diameter more than 4 cm. In MET-PET, a cut-off value of SUVmax is 5. On the basis of these criteria, FDG and MET identified lung cancer other than BAC with sensitivity of 89% (8/9), specificity of 96% (90/94). Our results suggest that quantitative assessment of uptake of FDG and MET

  13. Total cyanide mass measurement with micro-ion selective electrode for determination of specific activity of carbon-11 cyanide

    International Nuclear Information System (INIS)

    In this research, we aim to directly measure the specific activity (SA) of the carbon-11 cyanide ([11C]CN¯) produced by our in-house built automated [11C]HCN production system and to identify the major sources of 12C-cyanide (12CN¯). The [11C]CN¯ is produced from [11C]CO2, which is generated by the 14N(p,α)11C nuclear reaction using a cyclotron. Direct measurement of cyanide concentrations was accomplished using a relatively inexpensive, and easy to use ion selective electrode (ISE) which offered an appropriate range of sensitivity for detecting mass. Multiple components of the [11C]HCN production system were isolated in order to determine their relative contributions to 12CN¯ mass. It was determined that the system gases were responsible for approximately 30% of the mass, and that the molecular sieve/nickel furnace unit contributed approximately 70% of the mass. Beam on target (33 µA for 1 and 10 min) did not contribute significantly to the mass. Additionally, we compared the SA of our [11C]HCN precursor determined using the ISE to the SA of our current [11C]CN¯ derived radiotracers determined by HPLC to assure there was no significant difference between the two methods. These results are the first reported use of an ion selective electrode to determine the SA of no-carrier-added cyanide ion, and clearly show that it is a valuable, inexpensive and readily available tool suitable for this purpose. - Highlights: • Measurement of cyanide mass contribution from different component of automated [11C]HCN production system. • Determination of specific activity of [11C]HCN by micro ion selective electrode

  14. The ''in vivo'' distribution of carbon 11 labeled-nicotine in animals. A method suitable for use in man

    International Nuclear Information System (INIS)

    A method is described to label nicotine with carbon 11. A hundred millicuries can be obtained, in 45 minutes, with a high specific activity. This labeling of nicotine has allowed an ''in vivo'' study of the distribution of this very toxic drug in animals. Five minutes after injection in rabbits or monkeys, it was shown with a gamma camera or with a positron camera that the radioactivity was very rapidly distributed throughout the tissues especially in brain, lungs and kidneys. 11C-nicotine readily penetrates the blood-brain barrier and the brain radioactivity decreases very sharply with time. The eyes however retained activity, possibly in the retina. Unfortunately the monkey is not the ideal subject for 11C-nicotine brain study because: the brain is small, considering the resolution of the cameras and the cerebral lobes are also quite overlaped in this animal; Japanese authors have shown that compared with dogs the nicotine brain uptake is lower, due to the high affinity of nicotine for skeletal muscle which occupies approximately forty to fifty % of the body weight of the monkey. Also in monkeys, the nicotine destruction is faster than in dogs because there is a higher enzyme nicotine metabolizing activity in the liver of this animal. The differences observed between various animals studies using nicotine indicate that we should not draw any firm conclusions about the behaviour of this drug in humans. In order to do so, examinations must be conducted in man and the method described in spite of its limitations provides a means for such a study

  15. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Rolland, Marine; Skov, Peter V; Larsen, Bodil K; Holm, Jørgen; Gómez-Requeni, Pedro; Dalsgaard, Johanne

    2016-08-01

    Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter. The diets were fed in excess for six weeks before three sampling campaigns carried out successively to elucidate (i) the hepatic expression of selected genes involved in lipid, glucose and amino acid metabolism; (ii) the postprandial ammonia excretion; and (iii) the postprandial plasma methionine concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were significantly affected by the increase in dietary methionine. Changes in gene expression reflected to some extent the decrease in ammonia excretion (P=0.022) and in the hepatosomatic index (HSI; Ptrout responded in a dose-dependent manner to increasing levels of dietary methionine. PMID:27105833

  16. Your Pet's Medications

    Science.gov (United States)

    ... by Animal/Species Browse by Topic Browse by Discipline Resources VMA Resource Center Tools for K-12 ... infection because giving the preventive to a heartworm-positive pet will not treat the infection and could ...

  17. Clinical application of PET

    Energy Technology Data Exchange (ETDEWEB)

    Lomena, Francisco [Hospital Clinico Villarroel, Barcelona (Spain). Nuclear Medicine]. E-mail: flomena@clinic.ub.es; Soler, Marina [CETIR Grup Medic. Esplkugues de Llobregat, Barcelona (Spain). PET Unit

    2005-10-15

    Positron emission tomography (PET) is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluorodeoxyglucose-F 18 (FDG) PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.(author)

  18. Cold Weather Pet Safety

    Science.gov (United States)

    ... Emergency Care Animal Welfare Veterinary Careers Public Health Cold Weather Pet Safety Client Handout Available for download ... in hot cars , but did you know that cold weather also poses serious threats to your pets’ ...

  19. Combined PET/MRI

    DEFF Research Database (Denmark)

    Bailey, D. L.; Pichler, B. J.; Gückel, B.;

    2015-01-01

    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...... February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology......, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both...

  20. [Effects of L-methionine on nitrification and N2O emission in subtropical forest soil].

    Science.gov (United States)

    Lin, Wei; Pei, Guang-ting; Ma, Hong-liang; Gao, Ren; Yin, Yun-feng; Peng, Yuan-zhen

    2015-09-01

    The objective of this study was to investigate the influence of L-methionine on nitrification and nitrous oxide emission in a red soil under laboratory incubation experiments. A subtropical broad-leaved forest soil sample was collected from Wanmulin natural reserve in Fujian Province, Southeast China. Five treatments were carried out with three replications, i. e., control (CK), L- methionine addition (M), L-methionine and NH(4+)-N addition (MA), L-methionine and NO(2-)-N addition (MN), L-methionine and glucose addition (MC). The soil moisture was maintained at 60% WHC or 90% WHC. The results indicated that the soil NH(4+)-N content in the M treatment significantly increased by 0.8%-61.3%, while the soil NO(3-)-N content reduced by 13.2%-40.7% compared with CK. Under 60% WHC condition, soil NO(2-)-N content in the MC treatment was higher than in the M treatment, soil NO(3-)-N content in the MA and MN treatments were greater than that in the M treatment, and greater in the MN treatment than in the MA treatment. The soil NO(3-)-N content was lowest in the M treatment after incubation. These results suggested that L-methionine could inhibit nitrosation process of autotrophic nitrification. To some extent, carbon addition as glucose with L-methionine decreased the NH(4+)-N content, inhibited the autotrophic nitrification and their effects were dependent on water level. Under 90% WHC condition, carbon addition improved denitrification more obviously, but the decrease of NO(3-)-N content was not sufficient to prove the inhibition of hetero-nitrification due to carbon addition in the presence of L-methionine. The nitrous oxide emission from soil was increased by L-methionine addition. Compared with 60% WHC condition, the nitrous oxide emission was higher under 90% WHC condition, and the promotion of L-methionine addition on N2O was greater when glucose added. PMID:26785545

  1. Clinical application of pet

    OpenAIRE

    Francisco Lomeña; Marina Soler

    2005-01-01

    Positron emission tomography (PET) is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption ...

  2. A simple, versatile, low-cost and remotely operated apparatus for [11C]acetate, [11C]choline, [11C]methionine and [11C]PIB synthesis

    International Nuclear Information System (INIS)

    A simple, efficient and remotely operated synthesis apparatus for carrying out routine [11C]carboxylation, on-column and bubbling [11C]methylation was essential for reliable, day-to-day production of [11C]-labelled PET radiopharmaceuticals. We developed an in-house apparatus specifically applied to the synthesis of [11C]acetate, [11C]choline, [11C]methionine and 2-(4'-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB), where high radiochemical purity (≥97%) and moderate radiochemical yields (18% for [11C]PIB, 41-55% for the others) could be achieved. These findings provided evidence that this was a fast, versatile and reliable apparatus suitable for a PET/CT centre with limited financial budget and hot cell space for synthesis of [11C]-labelled radiopharmaceuticals

  3. Methionine enkephalin, its role in immunoregulation and cancer therapy.

    Science.gov (United States)

    Zhao, Dingliang; Plotnikoff, Nicolas; Griffin, Noreen; Song, Tao; Shan, Fengping

    2016-08-01

    Methionine enkephalin (MENK), an endogenous neuropeptide has a crucial role in both neuroendocrine and immune systems. MENK is believed to have an immunoregulatory activity to have cancer biotherapy activity by binding to the opioid receptors on immune and cancer cells. Clinical trial studies in cancer patients have shown that MENK activates immune cells directly and by inhibiting regulatory T-cells (Tregs). MENK may also change the tumor microenvironment by binding to opioid receptor on or in cancer cells. All of these mechanisms of action have biologic significance and potential for use in cancer immunotherapy. Furthermore, they reveal a relationship between the endocrine and immune systems. Due to the apparent role of MENK in cancer therapy we reviewed herein, the research undertaken with MENK in recent years; which has advanced our understanding of the role MENK has in cancer progression and its relationship to immunity, supporting MENK as a new strategy for cancer immunotherapy. PMID:26927200

  4. Methionine deficiency does not increase polyamine turnover through depletion of hepatic S-adenosylmethionine in juvenile Atlantic salmon.

    Science.gov (United States)

    Espe, Marit; Andersen, Synne Marte; Holen, Elisabeth; Rønnestad, Ivar; Veiseth-Kent, Eva; Zerrahn, Jens-Erik; Aksnes, Anders

    2014-10-28

    During the last few decades, plant protein ingredients such as soya proteins have replaced fishmeal in the diets of aquacultured species. This may affect the requirement and metabolism of methionine as soya contains less methionine compared with fishmeal. To assess whether methionine limitation affects decarboxylated S-adenosylmethionine availability and polyamine status, in the present study, juvenile Atlantic salmon were fed a methionine-deficient plant protein-based diet or the same diet supplemented with dl-methionine for 8 weeks. The test diets were compared with a fishmeal-based control diet to assess their effects on the growth performance of fish. Methionine limitation reduced growth and protein accretion, but when fish were fed the dl-methionine-supplemented diet their growth and protein accretion equalled those of fish fed the fishmeal-based control diet. Methionine limitation reduced free methionine concentrations in the plasma and muscle, while those in the liver were not affected. S-adenosylmethionine (SAM) concentrations were higher in the liver of fish fed the methionine-deficient diet, while S-adenosylhomocysteine concentrations were not affected. Putrescine concentrations were higher and spermine concentrations were lower in the liver of fish fed the methionine-deficient diet, while the gene expression of SAM decarboxylase (SAMdc) and the rate-limiting enzyme of polyamine synthesis ornithine decarboxylase (ODC) was not affected. Polyamine turnover, as assessed by spermine/spermidine acetyltransferase (SSAT) abundance, activity and gene expression, was not affected by treatment. However, the gene expression of the cytokine TNF-α increased in fish fed the methionine-deficient diet, indicative of stressful conditions in the liver. Even though taurine concentrations in the liver were not affected by treatment, methionine and taurine concentrations in muscle decreased due to methionine deficiency. Concomitantly, liver phospholipid and cholesterol

  5. Possible effects of delivering methionine to laying hens in drinking water

    Directory of Open Access Journals (Sweden)

    Sahin Cadirci

    2012-07-01

    Full Text Available Two experiments were conducted to study the effects of water-soluble DL-methionine supplied through water on the performance of laying hens. Two diet formulations were used in both experiments. For diet 1, nutrient specifications were set to meet or exceed requirements, whereas diet 2 was essentially diet 1 without supplemental methionine. Birds were divided into four groups of equal number. In experiment I, group 1 received diet 1 and normal water. Group 2, 3 and 4 received diet 2 and methionine treated water (0.050% for group 2; 0.075% for group 3; 0.100% for group 4. In experiment II, group 1 received diet 1 and normal water. Groups 2, 3 and 4 received diet 2 and methionine treated water (0.025% for group 2; 0.050% for group 3; 0.075% for group 4. In both experiments there were significant differences in egg weight and methionine intake between the groups, whereas no significant differences were observed in feed intake, water intake, egg production and feed conversation ratio. In the case of egg mass, significant differences between the treatment groups were found in experiment II but not in experiment I. The results suggest that the source of methionine does not influence its metabolic effect. Thus, it seems that methionine from the water is as good as when supplied wholly from the feed.

  6. Sulphur Atoms from Methionines Interacting with Aromatic Residues Are Less Prone to Oxidation

    Science.gov (United States)

    Aledo, Juan C.; Cantón, Francisco R.; Veredas, Francisco J.

    2015-11-01

    Methionine residues exhibit different degrees of susceptibility to oxidation. Although solvent accessibility is a relevant factor, oxidation at particular sites cannot be unequivocally explained by accessibility alone. To explore other possible structural determinants, we assembled different sets of oxidation-sensitive and oxidation-resistant methionines contained in human proteins. Comparisons of the proteins containing oxidized methionines with all proteins in the human proteome led to the conclusion that the former exhibit a significantly higher mean value of methionine content than the latter. Within a given protein, an examination of the sequence surrounding the non-oxidized methionine revealed a preference for neighbouring tyrosine and tryptophan residues, but not for phenylalanine residues. However, because the interaction between sulphur atoms and aromatic residues has been reported to be important for the stabilization of protein structure, we carried out an analysis of the spatial interatomic distances between methionines and aromatic residues, including phenylalanine. The results of these analyses uncovered a new determinant for methionine oxidation: the S-aromatic motif, which decreases the reactivity of the involved sulphur towards oxidants.

  7. PET and PET/CT in neuroendocrine tumours

    International Nuclear Information System (INIS)

    In the paper three modes of PET diagnostics are analyzed. Fluoro-deoxy-glucose (FDG)18F is recommended for evaluation of the most solid tumours. 18F DOPA PET with an aromatic aminoacid radiotracer is promising for studying neuroendocrine tumours (NET). Successes of PET of somatostatin receptors (SS-RPET) recently reported were mainly connected with high diagnostic accuracy achieved in NET tumours

  8. PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma

    International Nuclear Information System (INIS)

    Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes. Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of 18F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. 11C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET. Result: PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other. Conclusion: T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

  9. PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma

    Energy Technology Data Exchange (ETDEWEB)

    Nariai, Tadashi [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan)], E-mail: nariai.nsrg@tmd.ac.jp; Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Nakacho, Itabashi-ku, Tokyo (Japan); Kimura, Yuichi [Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba (Japan); Inaji, Motoki; Momose, Toshiya [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan); Yamamoto, Tetsuya; Matsumura, Akira [Department of Neurosurgery, University of Tsukuba, Tennodai, Tsukuba, Igaraki (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Nakacho, Itabashi-ku, Tokyo (Japan); Ohno, Kikuo [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan)

    2009-07-15

    Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes. Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of {sup 18}F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. {sup 11}C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET. Result: PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other. Conclusion: T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

  10. Autoradiographic visualization in comparison with the incorporation of 35S-methionine by various tissue protein

    International Nuclear Information System (INIS)

    The purpose of the present study was to observe the incorporation level of 35S-methionine by various tissue protein in organism. By the use of the macro- and micro-autoradiographic technique, the incorporation of 35S-methionine by the tissues has been utilized as an index of tissue protein synthesis. Further experiments showed that 35S-methionine was dominantly incorporated in the liver, kidney and spleen. It indicated that a strong protein metabolism produced in these tissues. In spite of the important physiological function of the heart, lung and skeletal muscle, the protein metabolism in those tissues was in a low level

  11. Gonadotropin hyperstimulation influences the 35S-methionine metabolism of mouse preimplantation embryos.

    Science.gov (United States)

    Wetzels, A M; Artz, M T; Goverde, H J; Bastiaans, B A; Hamilton, C J; Rolland, R

    1995-11-01

    The effects of gonadotropin stimulation on mouse embryo uptake and incorporation of 35S-methionine were studied. We found that the uptake of 35S-methionine was reduced in embryos of stimulated females in both the two-cell and the blastocyst developmental stage. The incorporation of 35S-methionine into protein was not statistically significantly different between the embryos of stimulated and those of unstimulated females. Qualitatively, protein synthesis was equal in both groups as determined with one-dimensional SDS-PAGE. The results are discussed and we conclude that mouse embryo viability in vivo is decreased by ovarian stimulation. PMID:8624434

  12. Identification and Functional Analysis of the Gene Encoding Methionine-γ-Lyase in Brevibacterium linens

    OpenAIRE

    Amarita, Felix; Yvon, Mireille; Nardi, Michele; Chambellon, Emilie; Delettre, Jerôme; Bonnarme, Pascal

    2004-01-01

    The enzymatic degradation of l-methionine and subsequent formation of volatile sulfur compounds (VSCs) is believed to be essential for flavor development in cheese. l-Methionine-γ-lyase (MGL) can convert l-methionine to methanethiol (MTL), α-ketobutyrate, and ammonia. The mgl gene encoding MGL was cloned from the type strain Brevibacterium linens ATCC 9175 known to produce copious amounts of MTL and related VSCs. The disruption of the mgl gene, achieved in strain ATCC 9175, resulted in a 62% ...

  13. Role of PET in Lymphoma

    OpenAIRE

    Markus Schwaiger; Hinrich Wieder

    2005-01-01

    In Hodgkin's lymphoma (HL), PET imaging should be performed in all patients, particularlyin stage I or II disease where change in staging will alter management. For aggressiveNon-Hodgkin's lymphoma (NHL), PET imaging is valuable to provide a baseline forresponse evaluation. For indolent NHL, it is concluded that PET imaging is not generallyindicated. For HL, a negative FDG-PET scan is highly indicative of long-term, disease-freesurvival and is particularly useful in the presence of residual C...

  14. Comparison of MET-PET and FDG-PET for differentiation between benign lesions and lung cancer in pneumoconiosis

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate and compare the ability of C-11-methionine (MET) and F-18 fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) to diagnose lung cancer in patients with pneumoconiosis. Twenty-six subjects underwent both wholebody MET-PET and FDG-PET on the same day. The first group was a lung cancer group, which consisted of 15 patients, and included those with pneumoconiosis with increased nodules (13 cases), hemoptysis (1 case), and positive sputum cytology (1 case). The second group was a no-malignancy control group, consisting of 11 patients with pneumoconiosis. Significant correlations between nodule size and the maximum standardized uptake value (SUVmax) of the two PET tracers were observed in the control group. The larger the nodule size, the greater were the amounts of these tracers accumulated (MET: r=0.771, Pmax of MET was significantly lower than that of FDG in the pneumoconiotic nodules (Pmax of MET was significantly higher in the lung cancer than in the pneumoconiotic nodules, with 3.48±1.18 (mean ± SE) for the lung cancer and 1.48±0.08 for the pneumoconiotic nodules (Pmax of FDG, with 7.12±2.36 and 2.85±0.24 (P<0.05), respectively. On the basis of the criteria for the control group, FDG and MET identified lung cancer with sensitivities of 60% and 80%, specificities of 100% and 93%, accuracies of 90% and 90%, positive predictive values of 100% and 80%, and negative predictive values of 88% and 93%, respectively. Our results indicate that nodules with an intense uptake of MET and FDG relative to their size should be carefully observed because of a high risk for lung cancer. (author)

  15. PET imaging of inflammation

    International Nuclear Information System (INIS)

    Inflammatory diseases are common place and often chronic. Most inflammatory cells have increased uptake of glucose which is enhanced in the presence of local cytokines. Therefore, imaging glucose metabolism by the means of 18F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) holds significant promise in imaging focal inflammation. Most of the work published involved small series of patients with either vasculitis, sarcoid or rheumatoid arthritis. It would appear that FDG PET is a simple and effective technique to identify inflammatory tissue in these conditions. There is even some work to suggest that by comparing baseline and early post therapy scans clinical outcome can be predicted. This would appear to be true with vasculitis as well as retroperitoneal fibrosis. The number of patients in each study is small but the evidence is compelling enough to recommend FDG PET imaging in the routine care of these patients.

  16. Novel PET sensors

    International Nuclear Information System (INIS)

    This thesis describes the design, synthesis and evaluation of novel molecular sensors that utilize the phenomena of Photoinduced Electron Transfer (PET). PET design can be incorporated into molecules to allow them to selectively bind certain guest molecules. PET works by the modulation of electron potentials within a molecule. Binding events between a host and guest can, if designed suitably, change these potentials enough to cause a transfer of electronic charge within the molecular sensor. This event can be accurately and sensitively monitored by the use of ultra violet or fluorescence spectroscopy. A sensor molecule can be constructed by matching the guest to a suitable receptor site and incorporating this into a molecule containing a fluorophore with the correct electron potential characteristics. By using existing synthetic routes as well as exploiting new pathways these sensor molecules C n be constructed to contain a fluorophore separated from a guest receptor(s) by suitable spacers units. When put together these facets go to creating molecules that by design are sensitive and selective for certain guest molecules or functional groups. This methodology allows the synthetic chemist to rationally design and synthesise PET sensors, tailored to the needs of the guest. In this thesis the synthesis and evaluation of a novel PET sensors for D-glucosamine, disaccharides and fluoride is presented. It is believed that the novel sensors using the PET phenomenon presented in this thesis are a worthwhile extension of previous works undertaken by other groups around the world and shows new pathways to increasingly complex and sophisticated sensor molecular design. (author)

  17. PET-CT; PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Schober, O. [Univeritaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Heindel, W. [Univeritaetsklinikum Muenster (Germany). Inst. fuer Klinische Radiologie

    2008-07-01

    Positron emission tomography - computerized tomography (PET-CT) is the fusion of two modern imaging techniques. The book includes the following chapters: 1. fundamentals: radiation protection aspects, radionuclide production, contrast agents, patient preparation, image interpretation; 2. diagnostics of carcinomas: carcinomas in brain, head-throat, thyroid, lungs, intestinal tract, gynecological carcinomas, urinary tract and bladder carcinomas, prostate carcinomas, malignant lymphomas, malignant malinomas, carcinomas in the skeletal system; 3. infections; 4. diagnostics of cardiovascular diseases; 5. diagnostics of neurodegenerative diseases; 6. developments and perspectives, 7. attachments: internet links, glossary, abbreviations.

  18. Carbon-11 labeled stilbene derivatives from natural products for the imaging of Aβ plaques in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Mengchao; Tang, Ruikun; Li, Zijing; Jia, Hongmei; Liu, Boli [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals; Zhang, Jinming; Zhang, Xiaojun [Chinese PLA General Hospital, Beijing (China). Dept. of Nuclear Medicine

    2014-04-01

    Four stilbene derivatives from natural products were screened as novel β-amyloid (Aβ) imaging ligands. In vitro binding assay showed that the methylated ligand, (E)-1-methoxy-4-styrylbenzene (8) displayed high binding affinity to Aβ{sub 1-42} aggregates (K{sub i} = 19.5 nM). Moreover, the {sup 11}C-labeled ligand, [{sup 11}C]8 was prepared through an O-methylation reaction using [{sup 11}C]CH{sub 3}OTf. In vitro autoradiography with sections of transgenic mouse brain also confirmed the high and specific binding of [{sup 11}C]8 to Aβ plaques. In vivo biodistribution experiments in normal mice indicated that [{sup 11}C]8 displayed high initial uptake (9.41 ± 0.51% ID/g at 5 min post-injection) into and rapid washout from the brain, with a brain{sub 5} {sub min}/brain{sub 30} {sub min} ratio of 6.63. These preliminary results suggest that [{sup 11}C]8 may be served as a novel Aβ imaging probe for PET. (orig.)

  19. Carbon-11 labeled stilbene derivatives from natural products for the imaging of Aβ plaques in the brain

    International Nuclear Information System (INIS)

    Four stilbene derivatives from natural products were screened as novel β-amyloid (Aβ) imaging ligands. In vitro binding assay showed that the methylated ligand, (E)-1-methoxy-4-styrylbenzene (8) displayed high binding affinity to Aβ1-42 aggregates (Ki = 19.5 nM). Moreover, the 11C-labeled ligand, [11C]8 was prepared through an O-methylation reaction using [11C]CH3OTf. In vitro autoradiography with sections of transgenic mouse brain also confirmed the high and specific binding of [11C]8 to Aβ plaques. In vivo biodistribution experiments in normal mice indicated that [11C]8 displayed high initial uptake (9.41 ± 0.51% ID/g at 5 min post-injection) into and rapid washout from the brain, with a brain5min/brain30min ratio of 6.63. These preliminary results suggest that [11C]8 may be served as a novel Aβ imaging probe for PET. (orig.)

  20. Clinical application of pet

    Directory of Open Access Journals (Sweden)

    Francisco Lomeña

    2005-10-01

    Full Text Available Positron emission tomography (PET is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT and magnetic resonance imaging (MRI, which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluordeoxyglucose-F18 (FDG PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.A tomografia por emissão de pósitrons (PET é uma técnica de diagnóstico por imagem que fornece informação sobre o metabolismo e funcionamento dos tecidos, diferente de outras técnicas de imagens como tomografia computadorizada (TC e ressonância magnética (RM, as quais fornecem informações estruturais ou anatômicas. O PET alcançou seu desenvolvimento em investigação biomédica devido à sua capacidade de usar traçadores análogos a muitas substâncias endógenas e de medir in vivo e de forma não invasiva seu consumo em diferentes órgãos e tecidos dos mamíferos 18Fluordesoxiglicose (FDG PET tem provado ser uma exploração de uso clínico com excelente relação custo benefício em oncologia e em muitas doenças neurológicas. Os atuais tomógrafos por PET-CT podem chegar a ser a melhor ferramenta de diagnóstico nos pacientes que sofrem de câncer.

  1. PET imaging of hypoxia

    International Nuclear Information System (INIS)

    Hypoxia in tumors has been related to poor response to conventional therapies. This paper will discuss the methods, both invasive and non-invasive, used to determine hypoxia levels within tumors. PET imaging with two lead compounds 18F-fluoro misonidazole (18FMISO) and Cu-(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) and their relative effectiveness in delineating hypoxic regions will be discussed. The advantages of Cu-ATSM-PET over existing imaging agents will be discussed along with its potential application as a direct-and/or surrogate marker for the determination of oncological hypoxia in vivo

  2. The percutaneous absorption of 35S-acetyl-L-methionine and L-serine in rabbit

    International Nuclear Information System (INIS)

    The authors had reported that L-cysteine probably was formed from acetyl-L-methionine and L-serine through cystathionine pathway by the skin enzyme of rabbit, and the solution composed of acetyl-L-methionine and L-serine exhibited the effectiveness to the hair growth in rabbit. This report shows that, by the application of 35S-acetyl-L-methionine and L-serine to the skin of rabbit and in vitro analysis of the metabolites of 35S-compounds, 35S-acetyl-L-methionine was absorbed into the hair tissues for many hours, and half 35S-L-cystine was formed in vitro and in vivo. When total amount of 35S in the hair was measured, the radiochemical activities were clearly shown as almost 35S-L-cystine. (auth.)

  3. Ferulic acid depletion by cultured soybean seedlings under action of glucose and methionine

    Directory of Open Access Journals (Sweden)

    Herrig Vanessa

    2000-01-01

    Full Text Available Cultured soybean seedlings were used to investigate how glucose or methionine influenced depletion of ferulic acid. Three-day-old seedlings were grown in hydroponic solution containing ferulic acid plus glucose or methionine, and the level of the phenolic acid were monitored in the nutrient culture. The results showed that ferulic acid depletion was more rapid in the presence of those compounds. After 6 h, the increase caused by glucose (0.01 and 0.05 mM was more pronounced than methionine in the same concentrations. On the other hand, methionine (0.1 and 0.2 mM increased depletion more significantly than glucose. Results suggested that both compounds might to increase the allelopathic effects of ferulic acid in the seedlings.

  4. Impact of methionine oxidation on calmodulin structural dynamics

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, Megan R.; Thompson, Andrew R.; Nitu, Florentin [Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, MN 55455 (United States); Moen, Rebecca J. [Chemistry and Geology Department, Minnesota State University, Mankato, MN 56001 (United States); Olenek, Michael J. [Biology Department, University of Wisconsin, La Crosse, WI 54601 (United States); Klein, Jennifer C., E-mail: jklein@uwlax.edu [Biology Department, University of Wisconsin, La Crosse, WI 54601 (United States); Thomas, David D., E-mail: ddt@umn.edu [Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, MN 55455 (United States)

    2015-01-09

    Highlights: • We measured the distance distribution between two spin labels on calmodulin by DEER. • Two structural states, open and closed, were resolved at both low and high Ca. • Ca shifted the equilibrium toward the open state by a factor of 13. • Methionine oxidation, simulated by glutamine substitution, decreased the Ca effect. • These results have important implications for aging in muscle and other tissues. - Abstract: We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of either M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron–electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous X-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM’s structural heterogeneity in solution: in both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ∼4 nm (closed) and another at ∼6 nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each

  5. Simultaneous PET and MR imaging

    International Nuclear Information System (INIS)

    We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2x2x10mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired. (author)

  6. Methionine synthase reductase deficiency results in adverse reproductive outcomes and congenital heart defects in mice

    OpenAIRE

    Deng, Liyuan; Elmore, C. Lee; Lawrance, Andrea K.; Matthews, Rowena G.; Rozen, Rima

    2008-01-01

    Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for pregnancy complications and birth defects. Methionine synthase reductase (MTRR) is required for activation of methionine synthase, a folate- and vitamin B12-dependent enzyme. A polymorphism in MTRR (p.I22M), present in the homozygous state in 25% of many populations, may increase risk for neural tube defects. To examine the impact of MTRR deficiency on early development and congenital heart defects, we u...

  7. A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity

    OpenAIRE

    Wang, Lien; Alachkar, Amal; Sanathara, Nayna; Belluzzi, James D.; Wang, Zhiwei; Civelli, Olivier

    2015-01-01

    Background: Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whe...

  8. The effect of methionine and 5-azacytidine on fragile X expression.

    OpenAIRE

    Abruzzo, M A; Mayer, M.; Jacobs, P A

    1985-01-01

    The cellular mechanism for the expression of the fragile site at Xq28 is unknown. We tested the effect of 5-azacytidine and methionine on fragile X expression in lymphocytes and lymphoblastoid cells in an attempt to determine if DNA methylation was involved. We were unable to demonstrate a consistent dosage effect of methionine on fragile X expression. While 5-azacytidine was found to inhibit the fragile X in both males and females, it did so only at relatively high concentrations. We conclud...

  9. Low-Dose Methotrexate Inhibits Methionine S-Adenosyltransferase In Vitro and In Vivo

    OpenAIRE

    Wang, Yi-cheng; Chiang, En-Pei Isabel

    2011-01-01

    Methionine S-adenosyltransferase (MAT) catalyzes the only reaction that produces the major methyl donor in mammals. Low-dose methotrexate is the most commonly used disease-modifying antirheumatic drug in human rheumatic conditions. The present study was conducted to test the hypothesis that methotrexate inhibits MAT expression and activity in vitro and in vivo. HepG2 cells were cultured under folate restriction or in low-dose methotrexate with and without folate or methionine supplementation....

  10. Methionine flux to transsulfuration is enhanced in the long living Ames dwarf mouse

    OpenAIRE

    Uthus, Eric O; Holly M. Brown-Borg

    2006-01-01

    Long-lived Ames dwarf mice lack growth hormone, prolactin, and thyroid stimulating hormone. Additionally the dwarf mice have enzyme activities and levels that combat oxidative stress more efficiently than those of normal mice. We have shown that methionine metabolism in Ames mice is markedly different than in their wild type littermates. In our previous work we hypothesized that the flux of methionine to the transsulfuration pathway is enhanced in the dwarf mice. The current study was designe...

  11. E. coli methionine sulfoxide reductase with a truncated N terminus or C terminus, or both, retains the ability to reduce methionine sulfoxide

    OpenAIRE

    Boschi-Muller, Sandrine; Azza, Saïd; Branlant, Guy

    2001-01-01

    The monomeric peptide methionine sulfoxide reductase (MsrA) catalyzes the irreversible thioredoxin-dependent reduction of methionine sulfoxide. The crystal structure of MsrAs from Escherichia coli and Bos taurus can be described as a central core of about 140 amino acids that contains the active site. The core is wrapped by two long N- and C-terminal extended chains. The catalytic mechanism of the E. coli enzyme has been recently postulated to take place through formation of a sulfenic acid i...

  12. Synthesis and evaluation of candidate PET radioligands for corticotropin-releasing factor type-1 receptors

    International Nuclear Information System (INIS)

    Introduction: A radioligand for measuring the density of corticotropin-releasing factor subtype-1 receptors (CRF1 receptors) in living animal and human brain with positron emission tomography (PET) would be a useful tool for neuropsychiatric investigations and the development of drugs intended to interact with this target. This study was aimed at discovery of such a radioligand from a group of CRF1 receptor ligands based on a core 3-(phenylamino)‐pyrazin-2(1H)-one scaffold. Methods: CRF1 receptor ligands were selected for development as possible PET radioligands based on their binding potency at CRF1 receptors (displacement of [125I]CRF from rat cortical membranes), measured lipophilicity, autoradiographic binding profile in rat and rhesus monkey brain sections, rat biodistribution, and suitability for radiolabeling with carbon-11 or fluorine-18. Two identified candidates (BMS-721313 and BMS-732098) were labeled with fluorine-18. A third candidate (BMS-709460) was labeled with carbon-11 and all three radioligands were evaluated in PET experiments in rhesus monkey. CRF1 receptor density (Bmax) was assessed in rhesus brain cortical and cerebellum membranes with the CRF1 receptor ligand, [3H]BMS-728300. Results: The three ligands selected for development showed high binding affinity (IC50 values, 0.3–8 nM) at CRF1 receptors and moderate lipophilicity (LogD, 2.8–4.4). [3H]BMS-728300 and the two 18F-labeled ligands showed region-specific binding in rat and rhesus monkey brain autoradiography, namely higher binding density in the frontal and limbic cortex, and cerebellum than in thalamus and brainstem. CRF1 receptor Bmax in rhesus brain was found to be 50–120 fmol/mg protein across cortical regions and cerebellum. PET experiments in rhesus monkey showed that the radioligands [18F]BMS-721313, [18F]BMS-732098 and [11C]BMS-709460 gave acceptably high brain radioactivity uptake but no indication of the specific binding as seen in vitro. Conclusions: Candidate CRF1

  13. Metabolic engineering of Corynebacterium glutamicum ATCC13032 to produce S-adenosyl-L-methionine.

    Science.gov (United States)

    Han, Guoqiang; Hu, Xiaoqing; Qin, Tianyu; Li, Ye; Wang, Xiaoyuan

    2016-02-01

    As an important biological methyl group donor, S-adenosyl-L-methionine is used as nutritional supplement or drug for various diseases, but bacterial strains that can efficiently produce S-adenosyl-L-methionine are not available. In this study, Corynebacterium glutamicum strain HW104 which can accumulate S-adenosyl-L-methionine was constructed from C. glutamicum ATCC13032 by deleting four genes thrB, metB, mcbR and Ncgl2640, and six genes metK, vgb, lysC(m), hom(m), metX and metY were overexpressed in HW104 in different combinations, forming strains HW104/pJYW-4-metK-vgb, HW104/pJYW-4-SAM2C-vgb, HW104/pJYW-4-metK-vgb-metYX, and HW104/pJYW-4-metK-vgb-metYX-hom(m)-lysC(m). Fermentation experiments showed that HW104/pJYW-4-metK-vgb produced more S-adenosyl-L-methionine than other strains, and the yield achieved 196.7 mg/L (12.15 mg/g DCW) after 48h. The results demonstrate the potential application of C. glutamicum for production of S-adenosyl-L-methionine without addition of L-methionine. PMID:26777246

  14. Healthy Pets and People

    Science.gov (United States)

    ... food and treats might include dry dog or cat food, dog biscuits, pig ears, beef hooves, and rodents ... after your pet, and before eating or preparing foods. Make sure to remove your ... contain dog or cat feces to prevent the spread of roundworms and ...

  15. Choosing a Pet

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    THE capital boasts countless markets of all kinds,but some of its insect,bird and pet markets immortalize Beijing culture and folkloric traditions.Don’t miss it! The Huasheng Tianqiao Market,south of the famous Panjiayuan Antique Market, was moved a few years ago and rebuilt in the

  16. PET Bottles Recycling

    Czech Academy of Sciences Publication Activity Database

    Veselý, Václav; Hanika, Jiří

    Praha : Ministry of Industry and Trade CR, 2008, s. 1-6. ISBN N. [Pollutec 2008. Lyon (FR), 02.12.2008-05.12.2008] R&D Projects: GA MPO FI-IM4/096 Institutional research plan: CEZ:AV0Z40720504 Keywords : pet recycling * waste * technical appliances Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  17. Total PET Recycling

    Czech Academy of Sciences Publication Activity Database

    Veselý, Václav; Punčochář, Miroslav

    Bratislava : Slovak University of Technology, 2004 - (Markoš, J.; Štefuca, V.), s. 222 ISBN 80-227-2052-6. [International Conference of Slovak Society of Chemical Engineering /31./. Tatranské Matliare (SK), 24.05.2004-28.05.2004] Institutional research plan: CEZ:AV0Z4072921 Keywords : recycling * waste management * pet Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  18. PET CT and lymphomas

    International Nuclear Information System (INIS)

    This presentation is about Tc and lymphomas. Classification and clinical cases of various cancer such as gastro duodenal or ulcer, mama, medullary, lymph and neck, leukemia, nodular sclerosis. Metabolic information, anatomical nature of lymphoma and its clinical presentation determine the extent that PET should be used in the patient.

  19. PET's indsats under lup

    DEFF Research Database (Denmark)

    Hansen, Peer Henrik

    2006-01-01

    En undersøgelseskommission nedsat i 1999. Fem medlemmer skal undersøge PET's efterretningsvirksomhed i forhold til politiske partier, faglige konflikter og politisk ideologiske bevægelser i Danmark under den kolde krig. Kommissionens rapport forventes færdig næste år. Udgivelsesdato: 2. juli 2006...

  20. PET and PET/CT in malignant melanoma; PET y PET/CT en melanoma maligno

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)

    2007-07-01

    The advantages that it has the PET/CT are: 1. It diminishes mainly positive false lesions. It identifies physiologic accumulate places. 2. It diminishes in smaller grade false negative. Small injuries. Injuries with low grade concentration. Injure on intense activity areas. 3. Precise anatomical localization of accumulate places. 4. Reduction of the acquisition time. (Author)

  1. Polyesteramides based on PET

    NARCIS (Netherlands)

    Bouma, Krista

    1999-01-01

    Engineering plastics have good mechanical, thermal and electrical properties, and can be easily processed. Typical engineering plastics include polyamides (PA6,6, PA6, PA4,6) and polyesters (PBT, PET). Compared to polyesters of a similar structure, polyamides have a high glass transition (Tg) and me

  2. I Love Petting Zoos!

    Centers for Disease Control (CDC) Podcasts

    2010-03-23

    This Kidtastics podcast helps children learn about how to stay safe and healthy when visiting petting zoos and other animal exhibits.  Created: 3/23/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/23/2010.

  3. Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis.

    Science.gov (United States)

    Ehlers, Tedman; Furness, Scott; Robinson, Thomas Philip; Zhong, Haizhen A; Goldsmith, David; Aribser, Jack; Bowen, J Phillip

    2016-01-01

    Angiogenesis has been identified as a crucial process in the development and spread of cancers. There are many regulators of angiogenesis which are not yet fully understood. Methionine aminiopeptidase is a metalloenzyme with two structurally distinct forms in humans, Type-1 (MetAP-1) and Type-2 (MetAP-2). It has been shown that small molecule inhibitors of MetAP-2 suppress endothelial cell proliferation. The initial discovery by Donald Ingber of MetAP-2 inhibition as a potential target in angiogenesis began with a fortuitous observation similar to the discovery of penicillin activity by Sir Alexander Fleming. From a drug design perspective, MetAP-2 is an attractive target. Fumagillin and ovalicin, known natural products, bind with IC50 values in low nanomolar concentrations. Crystal structures of the bound complexes provide 3-dimensional coordinates for advanced computational studies. More recent discoveries have shown other biological activities for MetAP-2 inhibition, which has generated new interests in the design of novel inhibitors. Semisynthetic fumagillin derivatives such as AGM-1470 (TNP-470) have been shown to have better drug properties, but have not been very successful in clinical trials. The rationale and development of novel multicyclic analogs of fumagillin are reviewed. PMID:26369821

  4. Methionine restriction on lipid metabolism and its possible mechanisms.

    Science.gov (United States)

    Zhou, Xihong; He, Liuqin; Wan, Dan; Yang, Huansheng; Yao, Kang; Wu, Guoyao; Wu, Xin; Yin, Yulong

    2016-07-01

    Methionine restriction (MR) exerts many beneficial effects, such as increasing longevity, decreasing oxidative damage and alleviating inflammatory responses. Much attention has been recently focused on the effects of MR on metabolic health, especially lipid metabolism, since the increasing incidence of obesity, insulin resistance and type 2 diabetes causes a worldwide health problem. In general, MR is considered to increase de novo lipogenesis, lipolysis and fatty acid oxidation, with a result of reduced fat accumulation. However, different responses in lipid metabolism between adipose tissue and liver are declared. Therefore, in this review, we will focus on the changes of lipid metabolism responses to dietary MR. Moreover, the comparison of alterations of fat metabolism responses to dietary MR between adipose tissue and liver, and the comparison of changes between rodents and pigs is made to illustrate the tissue- and species-specific responses. In addition, the possible mechanisms that might be engaged in the regulation of MR diet on lipid metabolism are also discussed. PMID:27156065

  5. The role of new PET tracers for lung cancer.

    Science.gov (United States)

    Szyszko, Teresa A; Yip, Connie; Szlosarek, Peter; Goh, Vicky; Cook, Gary J R

    2016-04-01

    18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer

  6. Methods of testing PET regenerates properties

    OpenAIRE

    2008-01-01

    The work presents an overview of the methods of testing poly(ethylene-terephthalate) (PET) regenerates: PET flakes, PET regranulates, PET preforms and PET bottles. All the methods have been included that are implemented for the quality testing of the mentioned products and allow constant control over the production process.

  7. 18F-FET-PET in Primary Hyperparathyroidism: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Martin Krakauer

    2016-08-01

    Full Text Available Preoperative localisation of the diseased parathyroid gland(s in primary hyperparathyroidism (PHP is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the 11C-based positron emission tomography (PET tracers methionine and choline have shown promise for this purpose. We evaluated the feasibility of using the 18F-based PET tracer fluoroethyl-l-tyrosine (FET, as the longer half-life of 18F makes it logistically more favourable. As a proof-of-concept study, we included two patients with PHP in which dual-isotope parathyroid subtraction single photon emission computed tomography had determined the exact location of the parathyroid adenoma. A dynamic FET PET/CT scan was performed with subsequent visual evaluation and calculation of target-to-background (TBR; parathyroid vs. thyroid. The maximum TBR in the two patients under study was achieved approximately 30 min after the injection of the tracer and was 1.5 and 1.7, respectively. This ratio was too small to allow for confident visualisation of the adenomas. FET PET/CT seems not feasible as a preoperative imaging modality in PHP.

  8. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

    Energy Technology Data Exchange (ETDEWEB)

    Neuner, Irene [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany); Kaffanke, Joachim B. [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); MR-Transfer e.K., Wuppertal (Germany); Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Neurology, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany)

    2012-12-15

    The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as {sup 18}F-fluoroethyl-l-tyrosine (FET) or {sup 11}C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

  9. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

    International Nuclear Information System (INIS)

    The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as 18F-fluoroethyl-l-tyrosine (FET) or 11C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

  10. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Rolland, Marine; Skov, Peter Vilhelm; Larsen, Bodil Katrine;

    2016-01-01

    Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signa...

  11. O-(2-[{sup 18}F]Fluoroethyl)-L-tyrosine and L-[methyl-{sup 11}C]methionine uptake in brain tumours: initial results of a comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.A.; Wester, H.J.; Herz, M.; Dzewas, B.; Stoecklin, G.; Schwaiger, M. [Dept. of Nuclear Medicine, Technische Univ. Muenchen (Germany); Grosu, A.L.; Feldmann, H.J.; Molls, M. [Department of Radiotherapy, Technische Universitaet Muenchen, Muenchen (Germany)

    2000-05-01

    O-(2-[{sup 18}F]Fluoroethyl)-l-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of l-[methyl-{sup 11}C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1{+-}0.2, 0.8{+-}0.2 and 2.7{+-}0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4{+-}0.2, 0.9{+-}0.1 and 3.3{+-}1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0{+-}0.1 SUV) was significantly lower than in tumour tissue (P=0.007). For all lesions there was a close correlation (r=0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions. (orig.)

  12. Modulation of cell cycle and gene expression in pancreatic tumor cell lines by methionine deprivation (methionine stress): implications to the therapy of pancreatic adenocarcinoma.

    Science.gov (United States)

    Kokkinakis, Demetrius M; Liu, Xiaoyan; Neuner, Russell D

    2005-09-01

    The effect of methionine deprivation (methionine stress) on the proliferation, survival, resistance to chemotherapy, and regulation of gene and protein expression in pancreatic tumor lines is examined. Methionine stress prevents successful mitosis and promotes cell cycle arrest and accumulation of cells with multiple micronuclei with decondensed chromatin. Inhibition of mitosis correlates with CDK1 down-regulation and/or inhibition of its function by Tyr(15) phosphorylation or Thr(161) dephosphorylation. Inhibition of cell cycle progression correlates with loss of hyperphosphorylated Rb and up-regulation of p21 via p53 and/or transforming growth factor-beta (TGF-beta) activation depending on p53 status. Although methionine stress-induced toxicity is not solely dependent on p53, the gain in p21 and loss in CDK1 transcription are more enhanced in wild-type p53 tumors. Up-regulation of SMAD7, a TGF-beta signaling inhibitor, suggests that SMAD7 does not restrict the TGF-beta-mediated induction of p21, although it may prevent up-regulation of p27. cDNA oligoarray analysis indicated a pleiotropic response to methionine stress. Cell cycle and mitotic arrest is in agreement with up-regulation of NF2, ETS2, CLU, GADD45alpha, GADD45beta, and GADD45gamma and down-regulation of AURKB, TOP2A, CCNA, CCNB, PRC1, BUB1, NuSAP, IFI16, and BRCA1. Down-regulation of AREG, AGTR1, M-CSF, and EGF, IGF, and VEGF receptors and up-regulation of GNA11 and IGFBP4 signify loss of growth factor support. PIN1, FEN1, and cABL up-regulation and LMNB1, AREG, RhoB, CCNG, TYMS, F3, and MGMT down-regulation suggest that methionine stress sensitizes the tumor cells to DNA-alkylating drugs, 5-fluorouracil, and radiation. Increased sensitivity of pancreatic tumor cell lines to temozolomide is shown under methionine stress conditions and is attributed in part to diminished O(6)-methylguanine-DNA methyltransferase and possibly to inhibition of the cell cycle progression. PMID:16170025

  13. Response of broiler strains differing in body fat to inadequate methionine: live performance and processing yields.

    Science.gov (United States)

    Moran, E T

    1994-07-01

    Ross x Arbor Acres (RxAA) and Steggles x Arbor (SxAA) chicks were given all nutrients as advocated by NRC (1984) except for methionine. Corn and soybean meal were the sole CP sources, and both strains were compared when feeds were adequate and deficient in methionine (0 to 3 wk, .65 vs .42% with 24.2% CP and 3.20 kcal AME/g; 3 to 6 wk, .54 vs .46% with 20.7% CP and 3.21 kcal AME; and 6 to 8 wk, .35 vs .30% with 17.8% CP and 3.19 kcal AME, respectively). Cystine exceeded NRC (1984) recommendation with all feeds. Live weights of RxAA broilers were heavier throughout the experiment, but SxAA had the advantage in feed conversion. Adverse effects of low methionine on weight gain were apparent only during the first 6 wk, and SxAA responded to the deficiency more than RxAA from 0 to 3 wk. The SxAA birds had less abdominal fat when processed at both 6 and 8 wk than RxAA. Low methionine increased fat proportions at 6 wk but not at 8 wk. Percentage chilled carcass yield without abdominal fat was similar for each strain and decreased as a result of low methionine at both ages. Low methionine also reduced proportions of skinless boneless breast meat but only at 6 wk and particularly in SxAA birds. The increased ability of RxAA birds to deposit fat enabled additional feed intake, in turn, minimizing repercussion of inadequate methionine. PMID:7937473

  14. Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thaliana proteins

    KAUST Repository

    Marondedze, Claudius

    2013-01-05

    Background: Increasing structural and biochemical evidence suggests that post-translational methionine oxidation of proteins is not just a result of cellular damage but may provide the cell with information on the cellular oxidative status. In addition, oxidation of methionine residues in key regulatory proteins, such as calmodulin, does influence cellular homeostasis. Previous findings also indicate that oxidation of methionine residues in signaling molecules may have a role in stress responses since these specific structural modifications can in turn change biological activities of proteins. Findings. Here we use tandem mass spectrometry-based proteomics to show that treatment of Arabidopsis thaliana cells with a non-oxidative signaling molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by cGMP-dependent methionine oxidation is functionally enriched for stress response proteins. Furthermore, we also noted distinct signatures in the frequency of amino acids flanking oxidised and un-oxidised methionine residues on both the C- and N-terminus. Conclusions: Given both a structural and functional bias in methionine oxidation events in response to a signaling molecule, we propose that these are indicative of a specific role of such post-translational modifications in the direct or indirect regulation of cellular responses. The mechanisms that determine the specificity of the modifications remain to be elucidated. 2013 Marondedze et al.; licensee BioMed Central Ltd.

  15. Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

    Institute of Scientific and Technical Information of China (English)

    Parameswaran; G; Sreekumar; David; R; Hinton; Ram; Kannan

    2011-01-01

    Methionine is a highly susceptible amino acid that can be oxidized to S and R diastereomeric forms of methionine sulfoxide by many of the reactive oxygen species generated in biological systems. Methionine sulfoxide reductases (Msrs) are thioredoxin-linked enzymes involved in the enzymatic conversion of methionine sulfoxide to methionine. Although MsrA and MsrB have the same function of methionine reduction, they differ in substrate specifi city, active site composition, subcellular localization, and evolution. MsrA has been localized in different ocular regions and is abundantly expressed in the retina and in retinal pigment epithelial (RPE) cells. MsrA protects cells from oxidative stress. Overexpression of MsrA increases resistance to cell death, while silencing or knocking down MsrA decreases cell survival; events that are mediated by mitochondria. MsrA participates in protein-protein interaction with several other cellular proteins. The interaction of MsrAwith α-crystallins is of utmost importance given the known functions of the latter in protein folding, neuroprotection, and cell survival. Oxidation of methionine residues in α-crystallins results in loss of chaperone function and possibly its antiapoptotic properties. Recent work from our laboratory has shown that MsrA is co-localized with αA and αB crystallins in the retinal samples of patients with age-related macular degen- eration. We have also found that chemically induced hypoxia regulates the expression of MsrA and MsrB2 in human RPE cells. Thus, MsrA is a critical enzyme that participates in cell and tissue protection, and its interaction with other proteins/growth factors may provide a target for therapeutic strategies to prevent degenerative diseases.

  16. PET in lung cancer staging

    International Nuclear Information System (INIS)

    The primary clinical application of FDG-PET is in the evaluation of patients with lung cancer and includes diagnosis, staging and restaging of non-small cell lung cancer. PET has a very high accuracy (sensitivity=97%, specificity=78%) for characterizing nodules that are indeterminate by chest radiograph and computed tomography. The major utility of PET in the evaluation of patients with lung cancer is the staging of the entire body. PET is more accurate than the conventional imaging modalities of CT and bone scans in the detection of metastatic disease. PET is accurate in the staging of the mediastinum, adrenal glands, and the skeletal system. PET is not as accurate in the detection of brain metastases because of their small size and the normal cortical accumulation

  17. Are Pets Good For Us?

    Institute of Scientific and Technical Information of China (English)

    邢连香

    2006-01-01

    A pet animal keeps us feel happy.Pets can staywith us when we are left by ourselves,and pets in-vite us to love and be loved.Often a cat or dog cankeep us easy at time when human words don’t help.Pets also keep us get close to the more natural animalworld.Learning to care for a pet helps a child to growup into a loving man or woman who feels responsible(有责任的) towards those dependent (依靠) on him.A pet dog can make us believe in others for we cansee faithfulness (忠诚) in the dog.In fact,we keeppets not only fo...

  18. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin;

    2012-01-01

    a number of different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation correction of PET. All MR techniques presented in this paper have shown promising results in the treatment of patients with solid......After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of...... the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to...

  19. Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.

    Science.gov (United States)

    Nicken, Petra; Empl, Michael T; Gerhard, Daniel; Hausmann, Julia; Steinberg, Pablo

    2016-09-01

    High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a -40%, a "normal" and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development. PMID:27427305

  20. Cyclotron/PET project in Uruguay

    International Nuclear Information System (INIS)

    The Positron Computed Tomography (PET) is a tri dimensional image technique which shows biochemical information. PET is used in neurology and cardiology diseases. The National Center Cyclotron PET has been found to research, development and health science applications.

  1. PET studies in dementia

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, K. [Neurologische Universitaetsklinik and Max-Planck-Inst. fuer neurologische Forschung, Koeln (Germany)

    2003-04-01

    Measurement of local cerebral glucose metabolism (lCMRGlc) by positron emission tomography (PET) and {sup 18}F-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard technique during the past 20 years and is now available at many university hospitals in all highly developed countries. Many studies have documented a close relation between lCMRGlc and localized cognitive functions, such as language and visuoconstructive abilities. Alzheimer's disease (AD) is characterized by regional impairment of cerebral glucose metabolism in neocortical association areas (posterior cingulate, temporoparietal and frontal multimodal association cortex), whereas primary visual and sensorimotor cortex, basal ganglia, and cerebellum are relatively well preserved. In a multicenter study comprising 10 PET centers (Network for Efficiency and Standardization of Dementia Diagnosis, NEST-DD) that employed an automated voxel-based analysis of FDG PET images, the distinction between controls and AD patients was 93% sensitive and 93% specific, and even in very mild dementia (at Mini Mental Status Examination (MMSE) 24 or higher) sensitivity was still 84% at 93% specificity. Significantly abnormal metabolism in mild cognitive deficit (MCI) indicates a high risk to develop dementia within the next two years. Reduced neocortical glucose metabolism can probably be detected with FDG PET in AD on average one year before onset of subjective cognitive impairment. In addition to glucose metabolism, specific tracers for dopamine synthesis ({sup 18}F-F-DOPA) and for ({sup 11}C-MP4A) are of interest for differentiation among dementia subtypes. Cortical acetylcholine esterase activity (AChE) activity is significantly lower in patients with AD or with dementia with Lewy bodies (DLB) than in age-matched normal controls. In LBD there is also impairment of dopamine synthesis, similar to Parkinson disease. (author) 115 refs.

  2. PET: active lymphoma?

    International Nuclear Information System (INIS)

    In the presented case, the PET (Positron Emission Tomography) has expired with several rolls. Firstly, it has been capable of detecting so much the infra-diaphragmatic illness not suspected after the initial treatment, as the persistence of illness in mediastinum. Later, it was helpful to face on the best place of biopsy in the mediastinum and to evaluate the situation of the patient after the treatment chemotherapeutic and the bone marrow transplantation

  3. Usage of Recycled Pet

    OpenAIRE

    A. Ebru Tayyar; Sevcan Üstün

    2010-01-01

    The increasing industrialization, urbanization and the technological development have caused to increase depletion of the natural resources and environmental pollution's problem. Especially, for the countries which have not enough space recycling of the waste eliminating waste on regular basis or decreasing the amount and volume of waste have provided the important advantages. There are lots of studies and projects to develop both protect resources and prevent environmental pollution. PET bot...

  4. PET studies in dementia

    International Nuclear Information System (INIS)

    Measurement of local cerebral glucose metabolism (lCMRGlc) by positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard technique during the past 20 years and is now available at many university hospitals in all highly developed countries. Many studies have documented a close relation between lCMRGlc and localized cognitive functions, such as language and visuoconstructive abilities. Alzheimer's disease (AD) is characterized by regional impairment of cerebral glucose metabolism in neocortical association areas (posterior cingulate, temporoparietal and frontal multimodal association cortex), whereas primary visual and sensorimotor cortex, basal ganglia, and cerebellum are relatively well preserved. In a multicenter study comprising 10 PET centers (Network for Efficiency and Standardization of Dementia Diagnosis, NEST-DD) that employed an automated voxel-based analysis of FDG PET images, the distinction between controls and AD patients was 93% sensitive and 93% specific, and even in very mild dementia (at Mini Mental Status Examination (MMSE) 24 or higher) sensitivity was still 84% at 93% specificity. Significantly abnormal metabolism in mild cognitive deficit (MCI) indicates a high risk to develop dementia within the next two years. Reduced neocortical glucose metabolism can probably be detected with FDG PET in AD on average one year before onset of subjective cognitive impairment. In addition to glucose metabolism, specific tracers for dopamine synthesis (18F-F-DOPA) and for (11C-MP4A) are of interest for differentiation among dementia subtypes. Cortical acetylcholine esterase activity (AChE) activity is significantly lower in patients with AD or with dementia with Lewy bodies (DLB) than in age-matched normal controls. In LBD there is also impairment of dopamine synthesis, similar to Parkinson disease. (author) 115 refs

  5. Pet Overpopulation: An Economic Analysis

    OpenAIRE

    Coate, Stephen; Knight, Brian

    2009-01-01

    This paper considers the problem of pet overpopulation. It develops a tractable dynamic model whose positive predictions square well with key features of the current U.S. market for pets. The model is used to understand, from a welfare economic perspective, the sense in which there is \\overpopulation" of pets and the underlying causes of the problem. The paper also employs the model to consider what policies might be implemented to deal with the problem. A calibrated example is developed to i...

  6. PETS 2014: dataset and challenge

    OpenAIRE

    Patino, Luis; Ferryman, James

    2015-01-01

    This paper describes the dataset and vision challenges that form part of the PETS 2014 workshop. The datasets are multisensor sequences containing different activities around a parked vehicle in a parking lot. The dataset scenarios were filmed from multiple cameras mounted on the vehicle itself and involve multiple actors. In PETS2014 workshop, 22 acted scenarios are provided of abnormal behaviour around the parked vehicle. The aim in PETS 2014 is to provide a standard benchmark that indicate...

  7. PET and Recycling

    Directory of Open Access Journals (Sweden)

    Funda Sevencan

    2007-08-01

    Full Text Available This review aims to clarify the need of decreasing the environmental effects caused by human and draw attention to the increasing environmental effects of plastics wastes. Plastics consist of organic molecules with high density molecules or polymers. Main resources of plastics are the residue of oil rafineries. Several advantages of plastics, have increased the usage continuously. Polyethylene Terephthalate (PET is the most commonly used plastics. PET is used to protect food, drinking water, fruit juice, alcoholic beverage, and food packing films. By the increasing interest on the environmental effects of plastic wastes, concerns on the recyclable packing materials also grew up. Also the daily use of recyclable containers consisting PET have increased. There are five steps for recycling of plastics. These steps are; using large amounts of plastics, collecting them in a big center, classifying and sorting the plastics, reproducing the polymers and obtaining new products with melted plastics. Providing a healthy recycling of plastics, the consumers should have knowledge and responsibility. The consumer should know what he/she has to do before putting the plastics in the recycling containers. Recycling containers and bags should be placed near the sources of plastic wastes. Consequently, the plastic wastes and environmental problems they cause will be on the agenda in future. [TAF Prev Med Bull. 2007; 6(4: 307-312

  8. [11C]Sorafenib: Radiosynthesis and preclinical evaluation in tumor-bearing mice of a new TKI-PET tracer

    International Nuclear Information System (INIS)

    Introduction: Tyrosine kinase inhibitors (TKIs) like sorafenib are important anticancer therapeutics with thus far limited treatment response rates in cancer patients. Positron emission tomography (PET) could provide the means for selection of patients who might benefit from TKI treatment, if suitable PET tracers would be available. The aim of this study was to radiolabel sorafenib (1) with carbon-11 and to evaluate its potential as TKI-PET tracer in vivo. Methods: Synthetic methods were developed in which sorafenib was labeled at two different positions, followed by a metabolite analysis in rats and a PET imaging study in tumor-bearing mice. Results: [methyl-11C]-1 and [urea-11C]-1 were synthesized in yields of 59% and 53%, respectively, with a purity of > 99%. The identity of the products was confirmed by coinjection on HPLC with reference sorafenib. In an in vivo metabolite analysis [11C]sorafenib proved to be stable. The percentage of intact product in blood–plasma after 45 min was 90% for [methyl-11C]-1 and 96% for [urea-11C]-1, respectively. Due to the more reliable synthesis, further research regarding PET imaging was performed with [methyl-11C]-1 in nude mice bearing FaDu (head and neck cancer), MDA-MB-231 (breast cancer) or RXF393 (renal cancer) xenografts. Highest tracer accumulation at a level of 2.52 ± 0.33 %ID/g was observed in RXF393, a xenograft line extensively expressing the sorafenib target antigen Raf-1 as assessed by immunohistochemistry. Conclusion: In conclusion, we have synthesized [11C]sorafenib as PET tracer, which is stable in vivo and has the capability to be used as PET tracer for imaging in tumor-bearing mice

  9. Positron emission tomography (PET) for cholangiocarcinoma

    OpenAIRE

    Breitenstein, S; Apestegui, C.; Clavien, P.-A.

    2008-01-01

    The combination of positron emission tomography (PET) with computed tomography (PET-CT) provides simultaneous metabolic and anatomic information on tumors in the same imaging session. Sensitivity of PET/PET-CT is higher for intrahepatic (>90%) than for extrahepatic cholangiocarcinoma (CCA) (about 60%). The detection rate of distant metastasis is 100%. PET, and particularly PET-CT, improves the results and impacts on the oncological management in CCA compared with other imaging modalities. The...

  10. RPC PET: Status and perspectives

    Science.gov (United States)

    Couceiro, M.; Blanco, A.; Ferreira, Nuno C.; Ferreira Marques, R.; Fonte, P.; Lopes, L.

    2007-10-01

    The status of the resistive plate chamber (RPC)-PET technology for small animals is briefly reviewed and its sensitivity performance for human PET studied through Monte-Carlo simulations. The cost-effectiveness of these detectors and their very good timing characteristics open the possibility to build affordable Time of Flight (TOF)-PET systems with very large fields of view. Simulations suggest that the sensitivity of such systems for human whole-body screening, under reasonable assumptions, may exceed the present crystal-based PET technology by a factor up to 20.

  11. Extended suicide with a pet.

    Science.gov (United States)

    Cooke, Brian K

    2013-01-01

    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases. PMID:24051598

  12. Determination of the specific activities of methionine sulfoxide reductase A and B by capillary electrophoresis.

    Science.gov (United States)

    Uthus, Eric O

    2010-06-01

    A capillary electrophoresis (CE) method for the determination of methionine sulfoxide reductase A and methionine sulfoxide reductase B activities in mouse liver is described. The method is based on detection of the 4-(dimethylamino)azobenzene-4'-sulfonyl derivative of l-methionine (dabsyl Met), the product of the enzymatic reactions when either dabsyl l-methionine S-sulfoxide or dabsyl l-methionine R-sulfoxide is used as a substrate. The method provides baseline resolution of the substrates and, therefore, can be used to easily determine the purity of the substrates. The method is rapid ( approximately 20min sample to sample), requires no column regeneration, and uses very small amounts of buffers. Separation was performed by using a 75-mum internal diameter polyimide-coated fused silica capillary (no inside coating) with 60cm total length (50cm to the detector window). Samples were separated at 22.5kV, and the separation buffer was 25mM KH(2)PO(4) (pH 8.0) containing 0.9ml of N-lauroylsarcosine (sodium salt, 30% [w/v] solution) per 100ml of buffer. Prior to use, the capillary was conditioned with the same buffer that also contained 25mM sodium dodecyl sulfate. The CE method is compared with high-performance liquid chromatography (HPLC) as determined by comparing results from measurements of hepatic enzyme activities in mice fed either deficient or adequate selenium. PMID:20167203

  13. A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity

    Science.gov (United States)

    Wang, Lien; Alachkar, Amal; Sanathara, Nayna; Belluzzi, James D.; Wang, Zhiwei

    2015-01-01

    Background: Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whether methionine administration could lead to behavioral changes that reflect schizophrenic symptoms in mice. Methods: l-Methionine was administered to mice twice a day for 7 days. Results: We found that this treatment induces behavioral responses that reflect the 3 types of schizophrenia-like symptoms (positive, negative, or cognitive deficits) as monitored in a battery of behavioral assays (locomotion, stereotypy, social interaction, forced swimming, prepulse inhibition, novel object recognition, and inhibitory avoidance). Moreover, these responses were differentially reversed by typical haloperidol and atypical clozapine antipsychotics in ways that parallel their effects in schizophrenics. Conclusion: We thus propose the l-methionine treatment as an animal model recapitulating several symptoms of schizophrenia. We have established the face and predictive validity for this model. Our model relies on an essential natural amino acid and on an intervention that is relatively simple and time effective and may offer an additional tool for assessing novel antipsychotics. PMID:25991655

  14. Suppression of Methionine Oxidation of a Pharmaceutical Antibody Stored in a Polymer-Based Syringe.

    Science.gov (United States)

    Masato, Amano; Kiichi, Fukui; Uchiyama, Susumu

    2016-02-01

    Oxidation of methionine residues is one of the well-known deteriorations in monoclonal antibody (mAb) therapeutics. Because methionine oxidation may affect their efficacy and pharmacokinetic profile, oxidation levels should be strictly controlled during their storage period. In this study, we revealed that when a therapeutic antibody was filled into a cyclo olefin polymer-based syringe and stored in a blister pack with an oxygen absorber, the methionine oxidation production under thermal or light stress was suppressed because of the reduction in the concentration of dissolved oxygen. Also unexpectedly, fewer amounts of the high-molecular-weight species and the acidic variants of the antibody were generated under thermal or light stress. Although the high-molecular-weight species contains methionine oxidants at similar levels to those in a monomer species, they were likely to be constituted from a higher amount of the oxidative species of internal disulfide linkage, tyrosine, or histidine. Because the dissolved oxygen could be readily removed from the mAb solution in the polymer-based syringe owing to its high gas permeability, this study shows the advantages of the polymer-based syringe with an oxygen absorber over glass syringes in terms of the suppression of the methionine oxidation and oxidative high molecular species. PMID:26462145

  15. Effect of folic acid on hematological changes in methionine-induced hyperhomocysteinemia in rats

    Directory of Open Access Journals (Sweden)

    Ansari M

    2009-01-01

    Full Text Available The present study was designed to investigate the effect of folic acid on homocysteine, lipid profile and hematological changes in methionine-induced hyperhomocysteinemic rats. Hyperhomocysteinemia was induced by methionine (1 g/kg, p.o. administration for 30 days. Biochemical and hematological observations were further substantiated with histopathological examination. The increase in homocysteine, total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and triglycerides levels with reduction in the levels of high density lipoprotein in serum were the salient features observed in methionine treated toxicologic control rats (i.e. group II. Hematological observations of the peripheral blood smears of toxicologic rats also showed crenation of red blood cells membrane and significant (P< 0.01 increase in total leukocyte count, differential leukocyte count and platelet counts with significant (P< 0.01 decrease in the mean hemoglobin levels, as compared to vehicle control rats. Administration of folic acid (100 mg/kg, p.o. for 30 days to methionine- induced hyperhomocysteinemic rats produced a significant (P< 0.01 decrease in the levels of homocysteine, total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and triglycerides with significant (P< 0.01 increase in high density lipoprotein-cholesterol levels in serum when compared with toxicologic control rats. The present study, for the first time, investigates the effect of folic acid treatment on hematological changes in rats with methionine-induced hyperhomocysteinemia.

  16. Regional distribution of methionine adenosyltransferase in rat brain as measured by a rapid radiochemical method

    International Nuclear Information System (INIS)

    The distribution of methionine adenosyltransferase (MAT) in the CNS of the rat was studied by use of a rapid, sensitive and specific radiochemical method. The S-adenosyl-[methyl-14C]L-methionine ([14C]SAM) generated by adenosyl transfer from ATP to [methyl-14C]L-methionine is quantitated by use of a SAM-consuming transmethylation reaction. Catechol O-methyltransferase (COMT), prepared from rat liver, transfers the methyl-14C group of SAM to 3,4-dihydroxybenzoic acid. The 14C-labelled methylation products, vanillic acid and isovanillic acid, are separated from unreacted methionine by solvent extraction and quantitated by liquid scintillation counting. Compared to other methods of MAT determination, which include separation of generated SAM from methionine by ion-exchange chromatography, the assay described exhibited the same high degree of specificity and sensitivity but proved to be less time consuming. MAT activity was found to be uniformly distributed between various brain regions and the pituitary gland of adult male rats. In the pineal gland the enzyme activity was about tenfold higher. (author)

  17. Effect of methionine and glucosamine conjugation on the anticancer activity of aromatic dinitrobenzamide mustards

    Indian Academy of Sciences (India)

    Karmakar Subhendu; Sudipta Bhattacharyya; Arindam Mukherjee

    2016-03-01

    Certain nutrients viz.,glucose and methionine are consumed more by cancer cells. Hence, an anticancer agent conjugated to them may render more toxicity in cancer cells due to higher uptake. To probe this effect, methionine and glucosamine were conjugated to a series of well-known aromatic dinitrobenzamide mustards. The in vitro cytotoxicity studies performed to probe the effect of such conjugation showed that the conjugation of methionine and glucosamine to one of the dinitrobenzamide mustard led to more toxicity selectively in human breast adenocarcinoma (MCF-7) cell lines. However, effect of functionalization cannot be generalized. Hypoxia based studies showed that IC50 value did not show much change from normoxic condition which is encouraging as many drugs deactivate in hypoxia. Among the glucosamine and methionine conjugated dinitrobenzamide mustards, the methionine conjugated aromatic dinitrobenzamide mustard of 2-chlorobenzoic acid is the most effective one. It acts by inducing apoptosis through G2/M phase arrest and encouragingly, is much less toxic to nontumorigenic human embryonic kidney (HEK-293T) and mouse embryonic fibroblast (NIH 3T3) cell lines in vitro.

  18. Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity.

    Science.gov (United States)

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M; Bortolato, Marco

    2014-10-01

    Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous single-nucleotide polymorphism (SNP) that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood post-translational mechanisms. One post-translational modification is methionine sulfoxide, which can be reduced by the methionine sulfoxide reductase (Msr) A and B enzymes. We used recombinant COMT proteins (Val/Met108) and mice (wild-type (WT) and MsrA knockout) to determine the effect of methionine oxidation on COMT activity and COMT interaction with Msr, through a combination of enzymatic activity and Western blot assays. Recombinant COMT activity is positively regulated by MsrA, especially under oxidative conditions, whereas brains of MsrA knockout mice exhibited lower COMT activity (as compared with their WT counterparts). These results suggest that COMT activity may be reduced by methionine oxidation, and point to Msr as a key molecular determinant for the modulation of COMT activity in the brain. The role of Msr in modulating cognitive functions in healthy individuals and schizophrenia patients is yet to be determined. PMID:24735585

  19. Cost-effectiveness of PET and PET/Computed Tomography

    DEFF Research Database (Denmark)

    Gerke, Oke; Hermansson, Ronnie; Hess, Søren; Schifter, Søren; Vach, Werner; Høilund-Carlsen, Poul Flemming

    2015-01-01

    measure by means of incremental cost-effectiveness ratios when considering the replacement of the standard regimen by a new diagnostic procedure. This article discusses economic assessments of PET and PET/computed tomography reported until mid-July 2014. Forty-seven studies on cancer and noncancer...

  20. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  1. Effects of Rumen Protected Methionine on Milk Yield and Milk Composition in Earlier Lactating Cow

    Institute of Scientific and Technical Information of China (English)

    SUN Manji; SHAN Anshan

    2008-01-01

    A total of 12 mature healthy Holstein dairy cows of the nearly body weight (580±30) kg, milk yield (22.5±2.8) kg in the early stages of lactation were selected in this experiment. The cows were randomly divided into 2 groups, every group had 6 cows, every group had 6 repeats, and every repeat had I cow. Added 20 g protected methionine in earlier lactating cow food every day. The results showed that protected methionine increased milk yield by 10.83%, testing group milk yield was significantly different than that of control (P<0.05);protected methionine increased milk fat by 5.98%, testing group milk fat was significantly different than that of control (P<0.05);Milk protein increased by 2.15%, but had insignificantly different (P>0.05);dry matter of milk had the tendency of decrease, but had insignificant difference (P>0.05).

  2. Studies on the shelf-life of L-35S methionine

    International Nuclear Information System (INIS)

    A systematic study conducted on the shelf -life of L-35S- methionine, an important radiotracer used in protein synthesis experiments is reported. Aliquots of 35S-methionine from bulk sample prepared by us were kept under chosen conditions of storage and were analysed by paper chromatography coupled with autoradiography. The radiochemical purity (RCP) of 35S-methionine at various time interval spanning over a period of about one half-life of 35S radioisotope (87.4 days) was determined. It was observed that the RCP came down only to about 89% from the original value of 96% at the end of the period of study under the chosen conditions. (author)

  3. Inhibition of the corrosion of carbon steel in HCl solution by methionine and its derivatives

    International Nuclear Information System (INIS)

    Highlights: • The methionine derivatives were good corrosion inhibitors for 1045 carbon steel (CS). • The XPS indicated that the FMOC self-assembled on CS surface by chemisorption. • The Fukui surface distribution and the radial distribution function were used. - Abstract: The self-assembled films of methionine and its derivatives were prepared on a 1045 carbon steel (CS) surface. EIS and potentiodynamic measurements showed that these films could effectively protect CS against corrosion in 0.5 M HCl, with a maximal protection efficiency of 95.01% achieved by FMOC films. An XPS study confirmed that methionine and its derivatives could form films by chemical adsorption on CS. The inhibition mechanism was theoretically investigated through the quantum chemical calculation and dynamic simulation

  4. Get Set for a Pet.

    Science.gov (United States)

    DeRosa, Bill

    1987-01-01

    Describes a game in which students deal with some of the factors involved in being a responsible pet owner. Includes a list of the materials needed for the game and provides the game board and the game pieces, along with a fold-out poster about neutering and spaying pets. (TW)

  5. Innovations in PET/CT

    DEFF Research Database (Denmark)

    Levin Klausen, T; Høgild Keller, S; Vinter Olesen, O;

    2012-01-01

    There has been a longstanding interest in positron emission tomography (PET) in combination with computed tomography (CT). Mostly because of the lack of structural information in PET which makes it difficult to assess the precise location of tissue with metabolic uptake, whereas CT can provide im...

  6. Neurotransmission imaging by PET

    International Nuclear Information System (INIS)

    PET studies on neurotransmission in psychological disorders to evaluate abnormal neurotransmission and therapeutic effects are thoroughly reviewed by type of major neurotransmitters. Studies on dopaminergic neurotransmission have focused on the function of dopamine D2 receptors, receptor subtypes, such as the D1 receptor, and ligands, such as transporters. PET studies of dopamine D2 receptor, which began in the early 1980s, have predominantly been performed in schizophrenia, and most have failed to detect any statistically significant differences between schizophrenia patients and controls. The studies in the early 1980s were performed by using [11C]N-methyl-spiperone (NMSP) and [11C]raclopride, ligands for striatal dopamine D2 receptors. [11C]FLB457, which has much higher affinity for D2 receptors than raclopride, began to be used in the 1990s. Dopamine D2 occupancy after drug ingestion has also been investigated to clarify the mechanisms and effects of antipsychotic drugs, and there have also been studies on the effect of aging and personality traits on dopamine D2 receptor levels in healthy subjects. In studies on dopamine receptor subtypes other than D2, dopamine D1 receptors have been studied in connection with assessments of cognitive functions. Most studies on dopamine transporters have been related to drug dependence. Serotonin 5-HT2A receptors have been studied with [11C]NMSP in schizophrenia patients, while studies of another serotonin receptor subtype, 5-HT1A receptors, have been mainly conducted in patients with depression. [11C]NMSP PET showed no difference between schizophrenia patients who had not undergone phamacotherapy and normal subjects. Because serotonin selective reuptake inhibitors (SSRIs) affect serotonin transporters, and abnormalities in serotonin transporters detected in mood disorders, PET ligands for serotonin transporters have increasingly been developed, and serotonin transporters have recently begun to be examined. GABA has been

  7. Neurotransmission imaging by PET

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    2001-08-01

    PET studies on neurotransmission in psychological disorders to evaluate abnormal neurotransmission and therapeutic effects are thoroughly reviewed by type of major neurotransmitters. Studies on dopaminergic neurotransmission have focused on the function of dopamine D{sub 2} receptors, receptor subtypes, such as the D{sub 1} receptor, and ligands, such as transporters. PET studies of dopamine D{sub 2} receptor, which began in the early 1980s, have predominantly been performed in schizophrenia, and most have failed to detect any statistically significant differences between schizophrenia patients and controls. The studies in the early 1980s were performed by using [{sup 11}C]N-methyl-spiperone (NMSP) and [{sup 11}C]raclopride, ligands for striatal dopamine D{sub 2} receptors. [{sup 11}C]FLB457, which has much higher affinity for D{sub 2} receptors than raclopride, began to be used in the 1990s. Dopamine D{sub 2} occupancy after drug ingestion has also been investigated to clarify the mechanisms and effects of antipsychotic drugs, and there have also been studies on the effect of aging and personality traits on dopamine D{sub 2} receptor levels in healthy subjects. In studies on dopamine receptor subtypes other than D{sub 2}, dopamine D{sub 1} receptors have been studied in connection with assessments of cognitive functions. Most studies on dopamine transporters have been related to drug dependence. Serotonin 5-HT{sub 2A} receptors have been studied with [{sup 11}C]NMSP in schizophrenia patients, while studies of another serotonin receptor subtype, 5-HT{sub 1A} receptors, have been mainly conducted in patients with depression. [{sup 11}C]NMSP PET showed no difference between schizophrenia patients who had not undergone phamacotherapy and normal subjects. Because serotonin selective reuptake inhibitors (SSRIs) affect serotonin transporters, and abnormalities in serotonin transporters detected in mood disorders, PET ligands for serotonin transporters have increasingly

  8. Functional and structural aspects of poplar cytosolic and plastidial type A methionine sulfoxide reductases

    OpenAIRE

    Rouhier, Nicolas; Kauffmann, Brice; Tete-Favier, Frédérique; Palladino, Pasquale; Gans, Pierre; Branlant, Guy; Jacquot, Jean-Pierre; Boschi-Muller, Sandrine

    2007-01-01

    The genome of Populus trichocarpa contains five methionine sulfoxide reductase A genes. Here, both cytosolic (cMsrA) and plastidial (pMsrA) poplar MsrAs were analyzed. The two recombinant enzymes are active in the reduction of methionine sulfoxide with either dithiothreitol or poplar thioredoxin as a reductant. In both enzymes, five cysteines, at positions 46, 81, 100, 196, and 202, are conserved. Biochemical and enzymatic analyses of the cysteine-mutated MsrAs support a catalytic mechanism i...

  9. Purification and Characterization of l-Methionine γ-Lyase from Brevibacterium linens BL2†

    OpenAIRE

    Dias, Benjamin; Weimer, Bart

    1998-01-01

    l-Methionine γ-lyase (EC 4.4.1.11) was purified to homogeneity from Brevibacterium linens BL2, a coryneform bacterium which has been used successfully as an adjunct bacterium to improve the flavor of Cheddar cheese. The enzyme catalyzes the α,γ elimination of methionine to produce methanethiol, α-ketobutyrate, and ammonia. It is a pyridoxal phosphate-dependent enzyme, with a native molecular mass of approximately 170 kDa, consisting of four identical subunits of 43 kDa each. The purified enzy...

  10. FE(II) Is the Native Cofactor for Escherichia coli Methionine Aminopeptidase*

    OpenAIRE

    Chai, Sergio C.; Wang, Wen-Long; Ye, Qi-Zhuang

    2008-01-01

    Divalent metal ions play a critical role in the removal of N-terminal methionine from nascent proteins by methionine aminopeptidase (MetAP). Being an essential enzyme for bacteria, MetAP is an appealing target for the development of novel antibacterial drugs. Although purified enzyme can be activated by several divalent metal ions, the exact metal ion used by MetAP in cells is unknown. Many MetAP inhibitors are highly potent on purified enzyme, but they fail to show si...

  11. Molecular characterization of the mde operon involved in L-methionine catabolism of Pseudomonas putida.

    OpenAIRE

    H. Inoue; Inagaki, K.; Eriguchi, S I; Tamura, T.; Esaki, N; Soda, K; Tanaka, H.

    1997-01-01

    A 15-kb region of Pseudomonas putida chromosomal DNA containing the mde operon and an upstream regulatory gene (mdeR) has been cloned and sequenced. The mde operon contains two structural genes involved in L-methionine degradative metabolism: the already-identified mdeA, which encodes L-methionine gamma-lyase (H. Inoue, K. Inagaki, M. Sugimoto, N. Esaki, K. Soda, and H. Tanaka. J. Biochem. (Tokyo) 117:1120-1125, 1995), and mdeB, which encodes a homologous protein to the homodimeric-type E1 co...

  12. Metabolism of excess methionine in the liver of intact rat: an in vivo 2H NMR study

    International Nuclear Information System (INIS)

    L-Methionine is the most toxic amino acid if supplied in excess, and the metabolic basis for this toxicity has been extensively studied, with varying conclusions. It is demonstrated here that in vivo 2H NMR spectroscopy provides a useful approach to the study of the hepatic metabolism of methionine in the anesthetized rat. Resonances corresponding to administered L-[methyl-2H3]methionine, and to the transmethylation product sarcosine, are observed during the first 10-min period after an intravenous injection of the labeled methionine, and the time dependence has been followed for a period of 5 h. A third resonance, assigned to the N-trimethyl groups of carnitine, phosphorylcholine, and other metabolites, becomes observable several hours after administration of the deuteriated methionine. In addition, there is a small increase in the intensity of the HDO resonance over the period of the study, which is interpreted to reflect the ultimate oxidation of the labeled sarcosine methyl group via mitochondrial sarcosine dehydrogenase. Additional small 2H resonances assigned to N1-methylhistidine and creatine could be observed in perchloric acid extracts of the livers of rats treated with the deuteriated methionine. Inhibition of the flux through the transmethylation pathway is observed in the rat pretreated with the S-ethyl analogue of methionine, ethionine. These data provide strong support for the importance of glycine transmethylation in the catabolism of excess methionine

  13. Nutritional levels of digestible methionine + cystine to brown-egg laying hens from 50 to 66 weeks of age

    Directory of Open Access Journals (Sweden)

    Clauber Polese

    2012-07-01

    Full Text Available The objective of this study was to determine the requirement of digestible methionine + cystine of brown-eggs laying hens from 50 to 66 weeks age at the end of the first production cycle. The design was completely randomized, with 150 Brown Shaver hens, which were distributed in five treatments with six replications of five birds each. Birds received a basal diet with 2857 kcal/kg metabolizable energy and 15.97% crude protein, supplemented with 0.132; 0.174, 0.215, 0.256 and 0.298% DL-methionine (98%, in order to provide 0.572, 0.613, 0.653, 0.693 and 0.734% digestible methionine + cystine. The levels of digestible methionine + digestible cystine followed, respectively, the relations of 67, 72, 77, 81 and 86% with lysine fixed at 0.851%. Feed intake, methionine + cystine intake, feed conversion per dozen eggs, egg weigth and mass, percentage of egg components, internal egg quality and weight gain were evaluated. Methionine + cystine levels showed a quadratic effect on feed conversion per dozen eggs and egg weight, a linear effect on feed conversion per kilogram of eggs and percentage of albumen. There was also a positive linear effect on yolk percentage. The methionine + cystine requirement was estimated at 0.572%, corresponding to 682 mg of digestible methionine + cystine/bird/day.

  14. Evaluation of PET Radioligands for the neuronal nicotinic acetylcholine receptor

    International Nuclear Information System (INIS)

    Full text: A-186253.1, a compound made by Abbott laboratories, was labelled with carbon-11 and evaluated as a PET ligand for the neuronal nicotinic acetylcholine receptor (nAChR). The compound was labelled with C-11 by methylation with 11C-MeI of the desmethyl precursor A-183828.1. The affinity of A-186253.1 for the α4β2 and the α7 subtype of the nAChR was determined in displacement studies. PET-studies were performed in rats and pigs Inhibitory constants (Ki) versus cytsine were 461 ± 99 pM for A-186253.1 and versus α-Bungarotoxin >100 μM. which means a very high selectivity for the α4β2-receptor (>227,000). Highest uptake of [11C]-A-186253.1 was observed in the thalamus where an increase in radiotracer uptake was seen until 45 min p.i.. Thereafter, the radiotracer concentration remained constant until the end of the scan indicating slow washout of [11C]-A-186253.1. Application of cold A-186253.1 (0.5 mg/kg) 40 min p.i. resulted in a decrease in radiotracer concentration in the thalamus and the cortex indicating displacement of [11C]-A-186253.1. Blockade studies with cytisine (0.5 mg/kg), a selective ligand for the α4β2 nicotinic receptor, showed just a slight reduction of the radioligand uptake in the thalamus and in the cortex whereas the blockade with cold A-186253.1 (1 mg/kg) resulted in a 50 % reduction. These results suggest, that 50 % of the [11C]-A-186253.1 in the brain corresponds to specifically bound radioligand, but not to the α4β2 subtype of the nicotinic receptor. (author)

  15. A novel, integrated PET-guided MRS technique resulting in more accurate initial diagnosis of high-grade glioma.

    Science.gov (United States)

    Kim, Ellen S; Satter, Martin; Reed, Marilyn; Fadell, Ronald; Kardan, Arash

    2016-06-01

    Glioblastoma multiforme (GBM) is the most common and lethal malignant glioma in adults. Currently, the modality of choice for diagnosing brain tumor is high-resolution magnetic resonance imaging (MRI) with contrast, which provides anatomic detail and localization. Studies have demonstrated, however, that MRI may have limited utility in delineating the full tumor extent precisely. Studies suggest that MR spectroscopy (MRS) can also be used to distinguish high-grade from low-grade gliomas. However, due to operator dependent variables and the heterogeneous nature of gliomas, the potential for error in diagnostic accuracy with MRS is a concern. Positron emission tomography (PET) imaging with (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) has been shown to add additional information with respect to tumor grade, extent, and prognosis based on the premise of biochemical changes preceding anatomic changes. Combined PET/MRS is a technique that integrates information from PET in guiding the location for the most accurate metabolic characterization of a lesion via MRS. We describe a case of glioblastoma multiforme in which MRS was initially non-diagnostic for malignancy, but when MRS was repeated with PET guidance, demonstrated elevated choline/N-acetylaspartate (Cho/NAA) ratio in the right parietal mass consistent with a high-grade malignancy. Stereotactic biopsy, followed by PET image-guided resection, confirmed the diagnosis of grade IV GBM. To our knowledge, this is the first reported case of an integrated PET/MRS technique for the voxel placement of MRS. Our findings suggest that integrated PET/MRS may potentially improve diagnostic accuracy in high-grade gliomas. PMID:27122050

  16. Differences in plasma metabolomics between sows fed DL-methionine and its hydroxy analogue reveal a strong association of milk composition and neonatal growth with maternal methionine nutrition.

    Science.gov (United States)

    Zhang, Xiaoling; Li, Hao; Liu, Guangmang; Wan, Haifeng; Mercier, Yves; Wu, Caimei; Wu, Xiuqun; Che, Lianqiang; Lin, Yan; Xu, Shengyu; Tian, Gang; Chen, Daiwen; Wu, De; Fang, Zhengfeng

    2015-02-28

    The aim of the present study was to determine whether increased consumption of methionine as DL-methionine (DLM) or its hydroxy analogue DL-2-hydroxy-4-methylthiobutanoic acid (HMTBA) could benefit milk synthesis and neonatal growth. For this purpose, eighteen cross-bred (Landrace × Yorkshire) primiparous sows were fed a control (CON), DLM or HMTBA diet (n 6 per diet) from 0 to 14 d post-partum. At postnatal day 14, piglets in the HMTBA group had higher body weight (P= 0·02) than those in the CON group, tended (P= 0·07) to be higher than those in the DLM group, and had higher (Phistidine and ornithine concentrations decreased in the DLM diet-fed sows (Pacetate and higher (P< 0·05) plasma levels of citrate, lactate, formate, glycerol, myo-inositol and N-acetyl glycoprotein in sows. Collectively, neonatal growth and milk synthesis were regulated by dietary methionine levels and sources, which resulted in marked alterations in amino acid, lipid and glycogen metabolism. PMID:25639894

  17. PET study of cholinergic system in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

    1999-01-01

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  18. PET study of cholinergic system in the brain

    International Nuclear Information System (INIS)

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  19. FDG PET imaging dementia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medical School and Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2007-04-15

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia.

  20. Neuropsychiatry: PET and SPECT

    International Nuclear Information System (INIS)

    Functional brain imaging with PET and SPECT have a definitive and well established role in the investigation of a variety of conditions such as dementia, epilepsy and drug addiction. With these methods it is possible to detect early rCBF (regional Cerebral Blood Flow) changes seen in dementia (even before clinical symptoms) and differentiate Alzheimer's disease from other dementias by means of the rCBF pattern change. 18-F-FDG PET imaging is a useful tool in partial epilepsy because both rCBF and brain metabolism are compromised at the epileptogenic focus. During the seizure, rCBF dramatically increases locally. Using SPECT it is possible to locate such foci with 97% accuracy. In drug addiction, particularly with cocaine, functional imaging has proven to be very sensitive to detect brain flow and metabolism derangement early in the course of this condition. These findings are important in many ways: prognostic value, they are used as a powerful reinforcement tool and to monitor functional recovery with rehabilitation. There are many other conditions in which functional brain imaging is of importance such as acute stroke treatment assessment, trauma rehabilitation and in psychiatric and abnormal movement diseases specially with the development of receptor imaging (au)

  1. FDG PET imaging dementia

    International Nuclear Information System (INIS)

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia

  2. PET AND PET-CT: PHYSICAL PRINCIPLE AND MEDICAL APLICATIONS

    OpenAIRE

    Rusu, V.; Cipriana Ştefănescu

    2007-01-01

    Positron emission tomography (PET) is a noninvasive imaging method that can “see” the metabolisms inside the living cells. It involves the acquisition of functional images based on the detection of radiation coming from the positron emission of a radiotracer administered to the patient. This radiotracer can be a metabolic analog, like is the case of glucose analog 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18FDG), the most commonly used PET radiotracer. PET images of the human body are used to...

  3. Positron emission tomography (PET) study of patients with pituitary adenoma using labeled amino acid

    Energy Technology Data Exchange (ETDEWEB)

    Mineura, Katsuyoshi; Sasajima, Toshio; Sakamoto, Tetsuya; Kowada, Masayoshi (Akita Univ. (Japan). Hospital); Shishido, Fumio; Uemura, Kazuo

    1989-12-01

    Four cases with pituitary adenomas were studied using {sup 11}C-L-methionine (C-11 Met) positron-emission tomography (PET). The C-11 Met was intravenously administered at a dose of 0.6 mCi/kg. The uptake of the tracer for tumors was calculated on the PET images 45 min after the injection; the uptake index was represented as a percentage of the total count in the arterial blood over a period of 45 min. In all cases, the C-11 Met accumulated intensely in the tumor regions; the PET images clearly delineated the extent of the tumor. The C-11 Met uptake index for pituitary adenomas varied widely from 3.94 x 10{sup -2}% to 15.36 x 10{sup -2}%, with a mean of 7.87 x 10{sup -2}%. These indices for the tumors increased markedly in comparison with that of the contralateral left temporal gray matter as a nontumor region (1.89 x 10{sup -2}% to 2.43 x 10{sup -2}% with a mean of 2.06 x 10{sup -2}%). In a case of prolactinoma, repeated PET following bromocriptine treatment showed a decrease in the C-11 Met uptake index; this decrease reflected changes in the serum prolactin value. In another case with ACTH-producing adenoma, the T/NT (tumor/nontumor) ratio fell from 3.44 to 2.40; however, the C-11 Met index remained unchanged. C-11 Met PET images facilitate determining the extent of pituitary adenomas and the monitoring of tumor response to treatment. Further application may give useful knowledge on the amino-acid metabolism of the tumor. (author).

  4. Positron emission tomography (PET) study of patients with pituitary adenoma using labeled amino acid

    International Nuclear Information System (INIS)

    Four cases with pituitary adenomas were studied using 11C-L-methionine (C-11 Met) positron-emission tomography (PET). The C-11 Met was intravenously administered at a dose of 0.6 mCi/kg. The uptake of the tracer for tumors was calculated on the PET images 45 min after the injection; the uptake index was represented as a percentage of the total count in the arterial blood over a period of 45 min. In all cases, the C-11 Met accumulated intensely in the tumor regions; the PET images clearly delineated the extent of the tumor. The C-11 Met uptake index for pituitary adenomas varied widely from 3.94 x 10-2% to 15.36 x 10-2%, with a mean of 7.87 x 10-2%. These indices for the tumors increased markedly in comparison with that of the contralateral left temporal gray matter as a nontumor region (1.89 x 10-2% to 2.43 x 10-2% with a mean of 2.06 x 10-2%). In a case of prolactinoma, repeated PET following bromocriptine treatment showed a decrease in the C-11 Met uptake index; this decrease reflected changes in the serum prolactin value. In another case with ACTH-producing adenoma, the T/NT (tumor/nontumor) ratio fell from 3.44 to 2.40; however, the C-11 Met index remained unchanged. C-11 Met PET images facilitate determining the extent of pituitary adenomas and the monitoring of tumor response to treatment. Further application may give useful knowledge on the amino-acid metabolism of the tumor. (author)

  5. Pioneering and fundamental achievements on the development of positron emission tomography (PET) in oncology

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG), a glucose analog, is widely used throughout the world as an indispensable imaging modality for the management of cancer treatment. This article reviews the pioneering achievements of PET in oncology with a focus on the development of PET that occurred from 1980 through the early-1990s. 18F-FDG was first applied for imaging of animal tumors in 1980 and for brain tumor imaging clinically in 1982. 18F-FDG enabled to visualize liver metastasis as clear positive image that could not be obtained by conventional nuclear imaging. Subsequently, 18F-FDG was used for imaging various cancers, such as lung, pancreas, colorectal and hepatoma. 11C-L-methionine (11C-MET) that reflects amino acid transport of cancers has an advantage that its uptake is lower in the brain and inflammatory tissue compared to 18F-FDG, and was first applied for imaging lung cancer and brain tumor. 18F-FDG and 11C-MET were proved to be sensitive tracers that can be used to objectively evaluate the effectiveness of cancer treatment. The diagnostic accuracy of PET, which is critical in clinical practice, was evaluated for the differential diagnosis of malignant and benign lung nodules using 18F-FDG or 11C-MET. In addition to 18F-FDG and 11C-MET, many radiopharmaceuticals were developed, such as 18F-labled thymidine analogs for evaluating proliferative activity, 18F-fluoromisonidazole for imaging of hypoxia, and 18F-fluorodeoxygalactose for evaluating liver-specific galactose metabolism and for imaging of hepatoma that retains galactose metabolic activity. These early efforts and achievements have greatly contributed to the development and clinical application of 18F-FDG PET in oncology. (author) 113 refs.

  6. Registration of SPECT, PET and/or X-ray CT images in patients with lung cancer

    International Nuclear Information System (INIS)

    Aim: In order to evaluate the therapeutic gain of heavy ion therapy performed on patients with lung cancer, the regional pulmonary functions and the amount of radio tracer accumulation to the tumor, we are investigated by using the region of interest based on anatomical information obtained from X-ray CT. There are many registration techniques for brain images, but not so much for the other organ images that we have studied registration of chest SPECT, PET and/or X-ray CT images. Materials and Methods: Perfusion, ventilation and blood pool images with Tc99m labeled radiopharmaceuticals and SPECT, tumor images with 11C-methionine and PET and X-ray CT scans were performed on several patients with lung cancer before and after heavy ion therapy. The registrations of SPECT-CT, PET-CT and CT-CT were performed by using AMIR (Automatic Multimodality Image Registration), which was developed by Babak et al. for registration of brain images. In a case of SPECT-CT registration, each of the three functional images was registered to the X-ray CT image, and the accuracy of each registration was compared. In the studies of PET-CT registration, the transmission images and X-ray CT images were registered at first, because the 11C-methionine PET images bear little resemblance to the underlying anatomical images. Next, the emission images were realigned by using the same registration parameters. The X-ray CT images obtained from a single subject at the different time were registered to the first X-ray CT images, respectively. Results: In the SPECT-CT registration, the blood pool-CT registration is the best among three SPECT images in visual inspection by radiologists. In the PET-CT registration, the Transmission-CT registrations got good results. Therefore, Emission-CT registrations also got good results. In the CT-CT registration, the X-ray CT images obtained from a single subject at the different time were superimposed well each other except for lower lobe. As the results, it was

  7. PET i prekirurgisk evaluering av epilepsi

    OpenAIRE

    2010-01-01

    PET in presurgical evaluation of epilepsy. Background: Today, at Rikshospitalet PET medical center, FDG is used as a tracer in the PET investigations during the presurgical evaluation of patients with epilepsy. The purpose of this paper is to see if FGD-PET gives additional information compared with EEG and MR. Another purpose was to find out whether there is a need for new ligands, and which ones. Material and methods: All epilepsy order forms to FDG-PET at Rikshopitalet, during 2007...

  8. Induction of Alzheimer's-like changes in brain of mice expressing mutant APP fed excess methionine.

    NARCIS (Netherlands)

    A. McCampbell; K. Wessner; M.W. Marlatt; C. Wolffe; D. Toolan; A. Podtelezhnikov; S. Yeh; R. Zhang; P. Szcerba; K.Q. Tanis; J. Majercak; W.J. Ray; M. Savage

    2011-01-01

    Elevated plasma homocysteine, a risk factor for Alzheimer's disease, could result from increased production from methionine or by inefficient clearance by folate- and B-vitamin-dependent pathways. Understanding the relative contributions of these processes to pathogenesis is important for therapeuti

  9. The First International Mini-Symposium on Methionine Restriction and Lifespan

    Directory of Open Access Journals (Sweden)

    Gene eAbles

    2014-05-01

    Full Text Available It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met ingestion by rats extends lifespan [1]. Since then, several studies have replicated the effects of dietary methionine restriction (MR in delaying age-related diseases [2–5]. We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY last September 2013. The goals were 1 to gather researchers with an interest in methionine restriction and lifespan, 2 to exchange knowledge, 3 to generate ideas for future investigations, and 4 to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH, and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g. the naked mole rat, Brandt’s bat and drosophila in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

  10. Platinum(II) complexes with steroidal esters of L-methionine and L-histidine

    Czech Academy of Sciences Publication Activity Database

    Kvasnica, Miroslav; Swaczynová, Jana; Kohout, Ladislav

    Ghent : Ghent University, 2008. s. 43. [BOSS 11. Belgian Organic Synthesis Symposium /11./. 13.07.2008-18.07.2008, Ghent] R&D Projects: GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z40550506 Keywords : platinum * L-methionine * L- histidine * cytotoxicity Subject RIV: CC - Organic Chemistry

  11. Prediction of (L)-methionine VCD spectra in the gas phase and water solution.

    Science.gov (United States)

    Rode, Joanna E; Dobrowolski, Jan Cz; Sadlej, Joanna

    2013-11-21

    In this paper we provide a computational study of the l-methionine conformational landscape and VCD spectra in the gas phase and a water environment simulated by implicit PCM and the hybrid model, i.e., a combination of explicit "microsolvation" and implicit models. In the gas phase, two groups of conformers differing in H-bonding, i.e., OH···NH2 and NH···O═C, could be distinguished based solely on the IR ν(OH) and ν(NH) stretching vibrations range. On the other hand, VCD better reflected chain differences. The most stable OH···NH2 conformer was predicted to be easily detected, and the presence of two out of four NH···O═C conformers could be confirmed. Three zwitterionic methionine conformers were shown to dominate in water. Their VCD spectra, simulated within the hybrid model at the B3LYP-IEF-PCM/aug-cc-pVDZ level of theory, indicated that they could be recognized in the mixture. Use of the hybrid model is crucial for good reproduction of the hydrogen bonding pattern in the VCD spectra of methionine in water solution. However, the 1300-800 cm(-1) region of the skeleton vibrations of methionine appeared to be relatively insensitive to the model of the solvent. PMID:24195697

  12. Acceleration of Selenium Volatilization in Seleniferous Agricultural Drainage Sediments Amended With Methionine and Casein.

    Science.gov (United States)

    Phytoremediation is a potential tool for the management of excessive Se in drainage sediment residing in the San Luis Drain in central California via plant extraction or biological volatilization of Se. This two-year field study in 2004/2005 examined the ability of organic amendments-methionine and ...

  13. Engineering of methionine chain elongation part of glucoraphanin pathway in E. coli

    DEFF Research Database (Denmark)

    Mirza, Nadia Muhammad Akram; Crocoll, Christoph; Olsen, Carl Erik;

    2016-01-01

    The methionine-derived glucosinolate glucoraphanin is associated with the health-promoting properties of broccoli. This has developed a strong interest in producing this compound in high amounts from a microbial source. Glucoraphanin synthesis starts with a five-gene chain elongation pathway that...

  14. PET/CT - Current status

    International Nuclear Information System (INIS)

    From autoradiography to planar X rays, computed tomography (CT) and Magnetic Resonance (MR), morphology and structure has been the mainstay of biological and medical imaging for over a century. While structural changes may suggest the presence of disease, functional changes are more sensitive indicators of early-stage pathology, and with cancer, early detection is the key to a favorable prognosis. Since molecular imaging offers the potential to quantitatively image functional changes in vivo, it is assuming an increasingly important role in the identification, staging and re-staging of human disease. Specifically, Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are sensitive techniques to map human physiology non-invasively through the use of high-resolution imaging devices and appropriate radioactively-labeled biomarkers. However, such metabolic maps do not offer the structural detail associated with anatomical imaging techniques such as CT and MR and therefore dual modality devices such as PET/CT, SPECT/CT or PET/MR that combine both structural and functional information offer a more complete and accurate assessment of the status of disease. PET/CT instrumentation, for example, was first introduced into the clinic in 2001 and since then, progress has been rapid. Technological advances in each modality, CT and PET, have been consistently incorporated into the combined device ensuring state-of-the-art performance for PET/CT. Recent advances in CT include an increase in the number of detector rows or slices (from 1 to 64), a reduction in rotation times (to less than 0.5 s), and the emergence of the first CT scanner incorporating dual X ray sources. Paralleling these advances, PET instrumentation has witnessed the introduction of new faster scintillators, higher resolution detectors, increased sensitivity through extended axial coverage, and the resurgence of time-of-flight information to improve image signal-to-noise. A

  15. Scintillation crystals required for PET

    International Nuclear Information System (INIS)

    In PET, inorganic scintillator crystals are used to record γ rays produced by the annihilation of positrons emitted by injected tracers. The ultimate performance of the camera is strongly tied to both the physical and scintillation properties of the crystals. For this reason, researchers have investigated virtually all known scintillator crystals for possible use in PET. Despite this massive research effort, only a few different scintillators have been found that have a suitable use. Two recently developed scintillator crystals (LSO and GSO), appears to surpass all previously used materials in most respects and promises to be the basis for the next generation of PET cameras. (authors)

  16. Methionine as a potential precursor for halogenated compounds by the reaction with iron minerals

    Science.gov (United States)

    Tubbesing, C.; Krause, T.; Mulder, I.; Kotte, K.; Schöler, H. F.

    2012-04-01

    Volatile halogenated compounds (VOX) play an important role in different photochemical reactions within the troposphere and the stratosphere. Soils and sediments seem to act as a major natural source for VOX, but investigations of the reaction mechanisms are rather scarce. To get further information on potential intermediates the reaction of the amino acid methionine with the ferrous and ferric iron minerals pyrite and ferrihydrite as well as solute ferrous sulfate was studied using a gas chromatography-flame ionization detector (GC-FID). Methionine is an important amino acid in the biosynthesis of plants used as a starting compound for the messenger ethene with aminocyclopropane carboxylic acid as an intermediate product. This pathway may also occur under abiotic conditions. Ethene is assumed as precursor for various halogenated C2-compounds like vinyl chloride and dichloroethene. Due to its ubiquity by an average concentration of 10 to 290 ng/g soil and its potential to regenerate in soils and organic litter by microorganisms, methionine may be an important educt for both abiotic and biotic terrestrial halogenation processes. In laboratory tests methionine was exposed to different iron species like pyrite, iron sulfate or ferrihydrite. The oxidant H2O2 was used to start the reaction. Production values of methyl chloride and other halogenated compounds are discussed in the context of methionine as their potential precursor and several Fe-minerals as soil-borne catalysers. Several possible intermediates for the production of VOX have been detected e.g. methane, ethene or propane. A formation of isobutylene is noteworthy for some cases. In addition to VOC the production of methyl chloride and dimethyl sulfide (DMS) was observed. Only the DMS bears upon a specific mineral. The samples containing pyrite reveal the highest concentrations. To get a better assessment of methionine, respectively VOC released from methionine as precursors for halogenated compounds

  17. PET and PET/CT in tumour of undetermined origin

    International Nuclear Information System (INIS)

    In this presentation the following conclusions were obtained regarding the use of PET and PET/CT in patient with cancer of unknown primary: 1. Detection of the primary one in 1/3 at 1/2 of patient. 2. It detects metastases in other places in 50%. 3. It changes the initial therapy planned in 1/3 at 1/2 of patient. 4. Useful in initial phases of protocol study to limit the other procedures. After standard evaluation. Before advanced protocol. 5. PET/CT study increases the % of primary detection, although in a non significant way vs. PET. 6. They are required more studies to value their utility to a more objective manner. (Author)

  18. Methionine kinetics and balance at the 1985 FAO/WHO/UNU intake requirement in adult men studied with L-[2H3-methyl-1-13C]methionine as a tracer

    International Nuclear Information System (INIS)

    The upper range of the requirement for methionine plus cystine in healthy adults was proposed in 1985 by FAO/WHO/UNU to be 13 mg.kg body wt-1.d-1. To explore the validity of this estimate, five healthy, young adult men were given for 7 d a diet based on an L-amino acid mixture supplying 13 mg methionine.kg-1.d-1 (87 mumol.kg-1.d-1) without cystine. Constant intravenous infusions of L-[2H3-methyl-1-13C]methionine were given on days 5 and 7 while subjects were in the fed and postabsorptive states, respectively. Estimates were made of methionine oxidation, and daily methionine balance was derived from the intake-oxidation data. For the five subjects, methionine balances were -0.9, +0.7, +3.5, -3.1, and -3.8 mg kg-1.d-1, or -6, +5, +23, -21, and -26 mumol.kg-1.d-1. These findings lead to the conclusion that the upper range of the requirement for methionine plus cystine probably exceeds 13 mg.kg-1.d-1 in healthy young adults. The implications of this conclusion for establishing an appropriate amount of sulfur amino acids in an amino acid requirement pattern for adults is discussed

  19. PET/TAC in Oncology; PET/TAC en Oncologia

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez V, A.M. [Especialista en Medicina Nuclear, Profa. Depto. Radiologia de la Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain)

    2007-07-01

    From this presentation of PET-TAC in oncology the following advantages on the conventional PET are obtained: 1. More short study and stadium in one session. 2. It adds the information of both techniques. 3. Better localization of leisure: affected organ, stadium change (neck, mediastinum, abdomen). 4. Reduction of false positive (muscle, brown fat, atelectasis, pneumonias, intestine, urinary vials, etc.). 5. Reduction of negative false. 6. Reduction of not conclusive. 7. More understandable for other specialists. 8. Biopsies guide. 9. Planning radiotherapy.

  20. Gender differences in methionine accumulation and metabolism in freshly isolated mouse hepatocytes: Potential roles in toxicity

    International Nuclear Information System (INIS)

    L-Methionine (Met) is hepatotoxic at high concentrations. Because Met toxicity in freshly isolated mouse hepatocytes is gender-dependent, the goal of this study was to assess the roles of Met accumulation and metabolism in the increased sensitivity of male hepatocytes to Met toxicity compared with female hepatocytes. Male hepatocytes incubated with Met (30 mM) at 37 oC exhibited higher levels of intracellular Met at 0.5, 1.0, and 1.5 h, respectively, compared to female hepatocytes. Conversely, female hepatocytes had higher levels of S-adenosyl-L-methionine compared to male hepatocytes. Female hepatocytes also exhibited higher L-methionine-L-sulfoxide levels relative to control hepatocytes, whereas the increases in L-methionine-D-sulfoxide (Met-D-O) levels were similar in hepatocytes of both genders. Addition of aminooxyacetic acid (AOAA), an inhibitor of Met transamination, significantly increased Met levels at 1.5 h and increased Met-D-O levels at 1.0 and 1.5 h only in Met-exposed male hepatocytes. No gender differences in cytosolic Met transamination activity by glutamine transaminase K were detected. However, female mouse liver cytosol exhibited higher methionine-DL-sulfoxide (MetO) reductase activity than male mouse liver cytosol at low (0.25 and 0.5 mM) MetO concentrations. Collectively, these results suggest that increased cellular Met accumulation, decreased Met transmethylation, and increased Met and MetO transamination in male mouse hepatocytes may be contributing to the higher sensitivity of the male mouse hepatocytes to Met toxicity in comparison with female mouse hepatocytes.

  1. Volatile sulphur compounds and pathways of L-methionine catabolism in Williopsis yeasts.

    Science.gov (United States)

    Tan, Amelia W J; Lee, Pin-Rou; Seow, Yi-Xin; Ong, Peter K C; Liu, Shao-Quan

    2012-08-01

    Volatile sulphur compounds (VSCs) are important to the food industry due to their high potency and presence in many foods. This study assessed for the first time VSC production and pathways of L: -methionine catabolism in yeasts from the genus Williopsis with a view to understanding VSC formation and their potential flavour impact. Five strains of Williopsis saturnus (var. saturnus, var. subsufficiens, var. suavolens, var. sargentensis and var. mrakii) were screened for VSC production in a synthetic medium supplemented with L: -methionine. A diverse range of VSCs were produced including dimethyl disulphide, dimethyl trisulphide, 3-(methylthio)-1-propanal (methional), 3-(methylthio)-1-propanol (methionol), 3-(methylthio)-1-propene, 3-(methylthio)-1-propyl acetate, 3-(methylthio)-1-propanoic acid (methionic acid) and ethyl 3-(methylthio)-1-propanoate, though the production of these VSCs varied between yeast strains. W. saturnus var. saturnus NCYC22 was selected for further studies due to its relatively high VSC production. VSC production was characterised step-wise with yeast strain NCYC22 in coconut cream at different L: -methionine concentrations (0.00-0.20%) and under various inorganic sulphate (0.00-0.20%) and nitrogen (ammonia) supplementation (0.00-0.20%), respectively. Optimal VSC production was obtained with 0.1% of L: -methionine, while supplementation of sulphate had no significant effect. Nitrogen supplementation showed a dramatic inhibitory effect on VSC production. Based on the production of VSCs, the study suggests that the Ehrlich pathway of L: -methionine catabolism is operative in W. saturnus yeasts and can be manipulated by adjusting certain nutrient parameters to control VSC production. PMID:22370952

  2. Utilization of zinc methionine supplementation in Friesian cows: somatic cell count in milk and mastitis

    International Nuclear Information System (INIS)

    Full text: Two hundreds and forty lactating Friesian cows on the 1st to 8th of lactation and different stages of lactation were used to study some factors affecting on somatic cell count and its effects on milk yield and composition. Also, 12 normal cows, 15 subclinical and 15 clinical mastitis cows were used to study the effect of zinc methionine supplementation on somatic cell count and mastitis. Cows were divided into three similar groups, the first groups was unsupplemented, while the second and third groups were supplemented with 5 and 10 gm zinc methionine / head / day, respectively. Subclinical and clinical mastitis cows were intramammary injected by antibiotic Gentamast (Gentamicin 100 mg) till complete recovery. The obtained results showed that winter season showed significantly (P < 0.05) the highest somatic cell count followed by summer season, while the lowest value was in autumn season. Somatic cell count tended to decrease with the progress of lactation up to the peak period and increased significantly (P < 0.05) thereafter and also with the progress number of lactation. The percentages of normal, subclinical and clinical mastitis cows were 77.71, 15.82 and 6.46%, respectively. Milk yield and composition and its output decreased significantly (P < 0.05) with increasing somatic cell count. Zinc methionine supplementation resulted in significant (P < 0.05) decrease in somatic cell count in milk. Zinc methionine supplementation for subclinical and clinical mastitis cows led to significant decrease (P < 0.05) on somatic cell count, electrical conductivity, recovery time and the cost of therapy compared with unsupplemented group. It could be concluded that increasing somatic cell count decreased milk yield and composition. Zinc methionine supplementation at the level of 5 g per head daily to lactating Friesian cows reduced somatic cell count in milk, recovery time and therapy cost of mastitis. (author)

  3. Parasites suppress immune-enhancing effect of methionine in nestling great tits.

    Science.gov (United States)

    Wegmann, Michèle; Voegeli, Beatrice; Richner, Heinz

    2015-01-01

    After birth, an organism needs to invest both in somatic growth and in the development of efficient immune functions to counter the effects of pathogens, and hence an investment trade-off is predicted. To explore this trade-off, we simultaneously exposed nestling great tits (Parus major) to a common ectoparasite, while stimulating immune function. Using a 2 × 2 experimental design, we first infested half of the nests with hen fleas (Ceratophyllus gallinae) on day 3 post-hatch and later, on day 9-13 post-hatch, and then supplemented half of the nestlings within each nest with an immuno-enhancing amino acid (methionine). We then assessed the non-specific immune response by measuring both the inflammatory response to a lipopolysaccharide (LPS) and assessing the levels of acute phase proteins (APP). In parasite-infested nestlings, methionine had a negative effect on body mass close to fledging. Methionine had an immune-enhancing effect in the absence of ectoparasites only. The inflammatory response to LPS was significantly lower in nestlings infested with fleas and was also lower in nestlings supplemented with methionine. These patterns of immune responses suggest an immunosuppressive effect of ectoparasites that could neutralise the immune-enhancing effect of methionine. Our study thus suggests that the trade-off between investment in life history traits and immune function is only partly dependent on available resources, but shows that parasites may influence this trade-off in a more complex way, by also inhibiting important physiological functions. PMID:25395313

  4. NEUROPSIQUIATRIA: PET Y SPECT

    Directory of Open Access Journals (Sweden)

    Juan Carlos Quintana F

    2002-01-01

    Full Text Available Existen numerosas indicaciones claramente establecidas para el uso del SPECT y PET en patología neuro-psiquiátrica, particularmente en el estudio de demencias, epilepsia y adicción a drogas. Estos métodos permiten detectar precozmente (aun antes de las manifestaciones clínicas cambios en la perfusión y metabolismo cerebral en pacientes con demencias. Es posible además diferenciar la enfermedad de Alzheimer de otras causas de demencia, analizando el patrón de la alteración neuro- funcional. En epilepsia parcial, tanto el metabolismo como la perfusión están alterados en el foco epileptogénico, lo que puede ser detectado con F-18FDG PET. Durante la crisis epiléptica, el flujo sanguíneo puede aumentar dramáticamente en el foco epileptogénico, lo que puede ser detectado con SPECT con 97% de certeza. En pacientes drogadictos, especialmente a la cocaína, estos métodos han demostrado ser muy sensibles para la detección precoz de cambios en el flujo y metabolismo cerebral, lo que es clínicamente importante en varios aspectos: 1 Tiene valor pronóstico (neuro-funcional, 2 Se puede usar para aumentar la adherencia a la terapia y 3 Permite evaluar objetivamente la recuperación funcional. Existen muchas otras indicaciones presentes y futuras, por ejemplo: en la monitorización de la revascularización en accidentes vasculares cerebrales agudos, rehabilitación post TEC, estudio de patología psiquiátrica y movimientos anormales especialmente con el desarrollo de radioligandosFunctional brain imaging with PET and SPECT have a definitive and well established role in the investigation of a variety of conditions such as dementia, epilepsy and drug addiction. With these methods it is possible to detect early rCBF (regional Cerebral Blood Flow changes seen in dementia (even before clinical symptoms and differentiate Alzheimer's disease from other dementias by means of the rCBF pattern change. 18-F-FDG PET imaging is a useful tool in partial

  5. Measuring PET scanner sensitivity

    International Nuclear Information System (INIS)

    Sensitivity parameters derived from a plot of a scanner's true coincidence count (TCC) rates as a function of activity in a 20 cm cylindrical phantom have no direct link to image quality. Noise equivalent count (NEC) rate curves, which incorporate the noise effects of subtracting the randoms and scatter count components provide a direct link between image signal-to-noise ratios and the scatter, randoms and trues coincidence count rates. The authors have measured TCC and NEC curves with a standardized 20 cm diameter nylon cylinder for five different PET scanners with several scanner-collimator combinations. In addition, the authors have compared TCC and NEC curves on one scanner with those from an Alderson brain phantom

  6. Methionine sulfoxide profiling of milk proteins to assess the influence of lipids on protein oxidation in milk.

    Science.gov (United States)

    Wüst, Johannes; Pischetsrieder, Monika

    2016-06-15

    Thermal treatment of milk and milk products leads to protein oxidation, mainly the formation of methionine sulfoxide. Reactive oxygen species, responsible for the oxidation, can be generated by Maillard reaction, autoxidation of sugars, or lipid peroxidation. The present study investigated the influence of milk fat on methionine oxidation in milk. For this purpose, quantitative methionine sulfoxide profiling of all ten methionine residues of β-lactoglobulin, α-lactalbumin, and αs1-casein was carried out by ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with scheduled multiple reaction monitoring (UHPLC-ESI-MS/MS-sMRM). Analysis of defatted and regular raw milk samples after heating for up to 8 min at 120 °C and analysis of ultrahigh-temperature milk samples with 0.1%, 1.5%, and 3.5% fat revealed that methionine oxidation of the five residues of the whey proteins and of residues M 123, M 135, and M 196 of αs1-casein was not affected or even suppressed in the presence of milk fat. Only the oxidation of residues M 54 and M 60 of αs1-casein was promoted by lipids. In evaporated milk samples, formation of methionine sulfoxide was hardly influenced by the fat content of the samples. Thus, it can be concluded that lipid oxidation products are not the major cause of methionine oxidation in milk. PMID:26927981

  7. [11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-0-methylation and initial small animal PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Riss, P.J.; Hooker, J.; Alexoff, D.; Kim, Sung-Won; Fowler, J.S.; Roesch, F.

    2009-05-01

    PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experiment demonstrates the reversible, highly specific binding of [{sup 11}C]PR04.MZ in the brain of a male Sprague-Dawley rat.

  8. Analysis of plasma metabolites during human PET studies with three receptor ligands, [11C]YM-09151-2, [11C]doxepin and [11C]pyrilamine

    International Nuclear Information System (INIS)

    Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D2 ligand [11C]YM-09151-2 as well as the histamine H1 ligands [11C]doxepin and [11C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [11C]YM-09151-2 and [11C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [11C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [11C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement. (author)

  9. Pets and the immunocompromised person

    Science.gov (United States)

    ... affect the cat's immune system. This puts your cat at risk of other infections that may be spread to humans. Feed your pet only commercially prepared food and treats. Animals can get sick from undercooked ...

  10. 10 "Poison Pills" for Pets

    Science.gov (United States)

    ... Care Animal Welfare Veterinary Careers Public Health 10 "Poison Pills" for Pets Anyone who takes medication prescribed ... of all phone calls to the ASPCA Animal Poison Control Center (APCC) are about human medications. Your ...

  11. PET and PET/CT in tumour of undetermined origin; PET y PET/CT en tumor de origen indeterminado

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging, PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)

    2007-07-01

    In this presentation the following conclusions were obtained regarding the use of PET and PET/CT in patient with cancer of unknown primary: 1. Detection of the primary one in 1/3 at 1/2 of patient. 2. It detects metastases in other places in 50%. 3. It changes the initial therapy planned in 1/3 at 1/2 of patient. 4. Useful in initial phases of protocol study to limit the other procedures. After standard evaluation. Before advanced protocol. 5. PET/CT study increases the % of primary detection, although in a non significant way vs. PET. 6. They are required more studies to value their utility to a more objective manner. (Author)

  12. 89Zr Radiochemistry for PET

    OpenAIRE

    Severin, G. W.; Engle, J W; Nickles, R.J.; Barnhart, T. E.

    2011-01-01

    The positron emitting isotope 89Zr is an ideal radiolabel for PET imaging of monoclonal antibodies (mAbs). This article reviews the chemistry and physics involved in production, separation, chelation, and labeling of 89Zr mAbs.

  13. Selecting Safe Pets (For Parents)

    Science.gov (United States)

    ... Reports? What to Say Vaccines: Which Ones & When? Smart School Lunches Emmy-Nominated Video "Cerebral Palsy: Shannon's ... pets. If you're interested in rabbits, the House Rabbit Society is an excellent resource — visit its ...

  14. Preventing Ticks on Your Pets

    Science.gov (United States)

    ... Tickborne diseases abroad Borrelia miyamotoi Borrelia mayonii Preventing ticks on your pets Recommend on Facebook Tweet Share ... your cats without first consulting your veterinarian! Kill Ticks on Dogs A pesticide product that kills ticks ...

  15. PET/CT and PET - application in pediatric oncology; PET/CT und PET - Einsatz in der paediatrischen Onkologie

    Energy Technology Data Exchange (ETDEWEB)

    Franzius, C.; Lang, K.; Schober, O. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Muenster (Germany); Wormanns, D. [Inst. fuer klinische Radiologie, Univ. Muenster (Germany); Vormoor, J. [Klinik und Poliklinik fuer Kinder- und Jugendmedizin - Paediatrische Haematologie und Onkologie, Univ. Muenster (Germany)

    2004-12-01

    PET-CT is a new imaging technology with a high capability to improve oncologic imaging. Introduction into clinical practise started approximately 3 years ago. Consequently, the available literature data are preliminary. There are no studies concerning PET-CT in pediatric patients. Nevertheless, it can already be supposed that the synthesis of structural and metabolic information improves the accuracy of staging and has the realistic potential to change patient management in a relevant percentage rate in pediatric patients. In this article, the advantages and special features of the application of PET-CT in young oncologic patients are pointed out. Potential clinical applications of PET-CT in this patient group include Hodgkin and non-Hodgkin lymphomas, Ewing tumors, osteosarcomas, rhabdomyosarcomas and neuroblastomas. (orig.)

  16. Disaster Preparedness for Your Pet

    Science.gov (United States)

    ... Do not let your pet interact with other animals Use disinfectant to clean the cage and litter box Leptospirosis is a bacterial disease found in the urine of infected animals that can cause kidney damage and affect other ...

  17. Radiation monitoring of PET staff

    International Nuclear Information System (INIS)

    Full text: Positron emission tomography (PET) is becoming a common diagnostic tool in hospitals, often located in and employing staff from the Nuclear Medicine or Radiology departments. Although similar in some ways, staff in PET departments are commonly found to have the highest radiation doses in the hospital environment due to unique challenges which PET tracers present in administration as well as production. The establishment of a PET centre with a dedicated cyclotron has raised concerns of radiation protection to the staff at the WA PET Centre and the Radiopharmaceutical Production and Development (RAPID) team. Since every PET centre has differing designs and practices, it was considered important to closely monitor the radiation dose to our staff so that improvements to practices and design could be made to reduce radiation dose. Electronic dosimeters (MGP DMC 2000XB), which have a facility to log time and dose at 10 second intervals, were provided to three PET technologists and three PET nurses. These were worn in the top pocket of their lab coats throughout a whole day. Each staff member was then asked to note down their duties throughout the day and also note the time they performed each duty. The duties would then correlate with the dose with which the electronic monitor recorded and an estimate of radiation dose per duty could be given. Also an estimate of the dose per day to each staff member could be made. PET nurses averaged approximately 20 μ8v per day getting their largest dose from caring for occasional problematic patients. Smaller doses of a 1-2 μ8v were recorded for injections and removing cannulas. PET technologists averaged approximately 15 μ8v per day getting their largest dose of 1-5μ8v mainly from positioning of patients and sometimes larger doses due to problematic patients. Smaller doses of 1-2 μ5v were again recorded for injections and removal of cannulas. Following a presentation given to staff, all WA PET Centre and RAPID staff

  18. Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway.

    Science.gov (United States)

    Mary, Camille; Duek, Paula; Salleron, Lisa; Tienz, Petra; Bumann, Dirk; Bairoch, Amos; Lane, Lydie

    2012-01-01

    The methionine salvage pathway is widely distributed among some eubacteria, yeast, plants and animals and recycles the sulfur-containing metabolite 5-methylthioadenosine (MTA) to methionine. In eukaryotic cells, the methionine salvage pathway takes place in the cytosol and usually involves six enzymatic activities: MTA phosphorylase (MTAP, EC 2.4.2.28), 5'-methylthioribose-1-phosphate isomerase (mtnA, EC 5.3.1.23), 5'-methylthioribulose-1-phosphate dehydratase (mtnB, EC: 4.2.1.109), 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase (mtnC, EC 3.1.3.77), aci-reductone dioxygenase (mtnD, EC 1.13.11.54) and 4-methylthio-2-oxo-butanoate (MTOB) transaminase (EC 2.6.1.-). The aim of this study was to complete the available information on the methionine salvage pathway in human by identifying the enzyme responsible for the dehydratase step. Using a bioinformatics approach, we propose that a protein called APIP could perform this role. The involvement of this protein in the methionine salvage pathway was investigated directly in HeLa cells by transient and stable short hairpin RNA interference. We show that APIP depletion specifically impaired the capacity of cells to grow in media where methionine is replaced by MTA. Using a Shigella mutant auxotroph for methionine, we confirm that the knockdown of APIP specifically affects the recycling of methionine. We also show that mutation of three potential phosphorylation sites does not affect APIP activity whereas mutation of the potential zinc binding site completely abrogates it. Finally, we show that the N-terminal region of APIP that is missing in the short isoform is required for activity. Together, these results confirm the involvement of APIP in the methionine salvage pathway, which plays a key role in many biological functions like cancer, apoptosis, microbial proliferation and inflammation. PMID:23285211

  19. Biometric Recognition for Pet Animal

    OpenAIRE

    Santosh Kumar; Sanjay Kumar Singh

    2014-01-01

    Missing, swapping, false insurance claims and reallocation of pet animals (dog) are global problems throughout the world and research done to solve this problem is minimal. Traditional biometrics and non-biometrics methods have their own boundaries and they fail to provide competent level of security to pet animal (dog). The work on animal identification based on their phenotype appearance (coat patterns) has been an active research area in recent years and automatic face recognition for...

  20. PET/TAC in Oncology

    International Nuclear Information System (INIS)

    From this presentation of PET-TAC in oncology the following advantages on the conventional PET are obtained: 1. More short study and stadium in one session. 2. It adds the information of both techniques. 3. Better localization of leisure: affected organ, stadium change (neck, mediastinum, abdomen). 4. Reduction of false positive (muscle, brown fat, atelectasis, pneumonias, intestine, urinary vials, etc.). 5. Reduction of negative false. 6. Reduction of not conclusive. 7. More understandable for other specialists. 8. Biopsies guide. 9. Planning radiotherapy

  1. Nutritional sustainability of pet foods.

    Science.gov (United States)

    Swanson, Kelly S; Carter, Rebecca A; Yount, Tracy P; Aretz, Jan; Buff, Preston R

    2013-03-01

    Sustainable practices meet the needs of the present without compromising the ability of future generations to meet their needs. Applying these concepts to food and feed production, nutritional sustainability is the ability of a food system to provide sufficient energy and essential nutrients required to maintain good health in a population without compromising the ability of future generations to meet their nutritional needs. Ecological, social, and economic aspects must be balanced to support the sustainability of the overall food system. The nutritional sustainability of a food system can be influenced by several factors, including the ingredient selection, nutrient composition, digestibility, and consumption rates of a diet. Carbon and water footprints vary greatly among plant- and animal-based ingredients, production strategy, and geographical location. Because the pet food industry is based largely on by-products and is tightly interlinked with livestock production and the human food system, however, it is quite unique with regard to sustainability. Often based on consumer demand rather than nutritional requirements, many commercial pet foods are formulated to provide nutrients in excess of current minimum recommendations, use ingredients that compete directly with the human food system, or are overconsumed by pets, resulting in food wastage and obesity. Pet food professionals have the opportunity to address these challenges and influence the sustainability of pet ownership through product design, manufacturing processes, public education, and policy change. A coordinated effort across the industry that includes ingredient buyers, formulators, and nutritionists may result in a more sustainable pet food system. PMID:23493530

  2. Bio-efficacy comparison of herbal-methionine and DL-methionine based on performance and blood parameters of broiler chickens

    Directory of Open Access Journals (Sweden)

    Sheila Hadinia

    2014-06-01

    Full Text Available This study was conducted to compare the bio-efficacy of herbal methionine (H-Met relative to DL-methionine (DL-Met on 160 “Ross 308” broiler chickens. DL-Met and H-Met were added to the basal diet in eight experimental treatments with three and four concentrations respectively in starter, grower and finisher period. Blood parameters which were measured at 24 and 42 days of age consisted of: serum proteins (total protein, albumin and globulin, serum uric acid, serum fats (low density lipoprotein, high density lipoprotein, triglyceride and cholesterol and serum enzymes (alanine amino transaminase and aspartate amino transaminase. Completely randomized design, multi-exponential and multilinear regressions were used to determine bio-efficacy of H-Met in terms of performance and blood parameters of broilers. The results showed that supplemented methionine (Met sources had no significant effect on blood parameters at 24 day of age. At 42 day of age the amounts of globulin and serum high density lipoprotein (HDL increased with supplemented Met, (p < 0.05. Regression analysis revealed that H-Met was 55.00, 71.00, 78.00, 47.00, 58.00 and 73.00% as efficacious as DL-Met for body weight gain, feed intake, feed conversion ratio, albumin, globulin and high density lipoprotein criteria, respectively. The average of bio-efficacy of H-Met compared to DL-Met was 67.00% and 59.00% on average across performance criteria and blood criteria respectively and was 63.00% across these two criteria tested. The results of the present study indicated that H-Met can be administered as a new and a natural source of Met in poultry industry.

  3. PET AND PET-CT: PHYSICAL PRINCIPLE AND MEDICAL APLICATIONS

    Directory of Open Access Journals (Sweden)

    V.Rusu

    2007-04-01

    Full Text Available Positron emission tomography (PET is a noninvasive imaging method that can “see” the metabolisms inside the living cells. It involves the acquisition of functional images based on the detection of radiation coming from the positron emission of a radiotracer administered to the patient. This radiotracer can be a metabolic analog, like is the case of glucose analog 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18FDG, the most commonly used PET radiotracer. PET images of the human body are used to evaluate a variety of diseases, most often to detect cancer and to examine the effects of cancer therapy by characterizing cell viability and biochemical changes in the cell. It is potentially useful in cancer imaging because the increased metabolism of tumor cells leads to increased uptake of glucose, and, therefore, uptake of 18FDG, also. PET-CT is the fusion of functional and anatomic information acquired almost simultaneously, that lets us see both the structural anatomy and the functional data on the same image. They complete each other: if PET scan is powerful in evaluating the functional characteristics of the tissues, CT is a powerful structural resolution imaging method. The highly sensitive PET scan detects the metabolic signal of actively growing cancer cells in the body and the CT scan provides a detailed picture of the internal anatomy that reveals sites, size and shape of cancer tissue. Alone, each imaging test has particular benefits and limitations but when the results of PET and CT scans are "fused" together, the combined image provides complete information on cancer location and metabolism.

  4. Improved automated synthesis and preliminary animal PET/CT imaging of 11C-acetate

    International Nuclear Information System (INIS)

    To study a simple and rapid automated synthetic technology of 11C-acetate (11C- AC), automated synthesis of 11C-AC was performed by carboxylation of MeMgBr/tetrahydrofuran (THF) on a polyethylene loop with 11C-CO2, followed by hydrolysis and purification on solid-phase extraction cartridges using a 11C-Choline/Methionine synthesizer made in China. A high and reproducible radiochemical yield of above 40% (decay corrected) was obtained within the whole synthesis time about 8 min from 11C-CO2. The radiochemical purity of 11C-AC was over 95%. The novel, simple and rapid on-column hydrolysis-purification procedure should adaptable to the fully automated synthesis of 11C-AC at several commercial synthesis module. 11C-AC injection produced by the automated procedure is safe and effective, and can be used for PET imaging of animals and humans. (authors)

  5. Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, l-methionine, {sup 67}Ga-citrate, and {sup 125}I-HSA

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Y.; Gutowski, T.D.; Fisher, S.J.; Brown, R.S. [Michigan Univ., Ann Arbor (United States). Medical Center; Wahl, R.L. [Michigan Univ., Ann Arbor (United States). Medical Center]|[Department of Radiology, University of Michigan Medical Center, Ann Arbor (United States)

    1999-04-29

    The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-d-glucose (FDG), thymidine, and l-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of {sup 18}F- or {sup 3}H-FDG, {sup 3}H-thymidine, l-{sup 11}C- or {sup 3}H-methionine, gallium-67 citrate ({sup 67}Ga-citrate) and iodine-125 human serum albumin ({sup 125}I-HSA) was determined in these animals. {sup 3}H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although {sup 18}F-FDG, {sup 67}Ga-citrate, and {sup 125}I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g) x kg at 2 h postinjection was as follows: {sup 18}F-FDG, 0.184{+-}0.026 to 0.218{+-}0.046; {sup 67}Ga-citrate, 0.221{+-}0.016; {sup 125}I-HSA, 0.198{+-}0.019], the infected muscle to blood ratio was much higher for {sup 18}F-FDG than for {sup 67}Ga-citrate or {sup 125}I-HSA ({sup 18}F-FDG, 10.31{+-}0.76 to 14.89{+-}2.26; {sup 67}Ga-citrate, 1.24{+-}0.67; {sup 125}I-HSA, 0.20{+-}0.02). The draining reactive lymph nodes also showed higher accumulation of {sup 18}F-FDG than of {sup 67}Ga-citrate or {sup 125}I-HSA. The uptake of {sup 3}H-thymidine and l-{sup 11}C- or {sup 3}H-methionine in the infected muscle was lower than that of {sup 18}F- or {sup 3}H-FDG at 2 h postinjection, {sup 3}H-thymidine = 0.039{+-}0.005 and L-{sup 3}H-methionine = 0.063{+-}0.007 (%ID/g) x kg. Autoradiographs showed that the highest {sup 3}H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, {sup 18}F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be

  6. Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, l-methionine, 67Ga-citrate, and 125I-HSA

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-d-glucose (FDG), thymidine, and l-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, l-11C- or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g) x kg at 2 h postinjection was as follows: 18F-FDG, 0.184±0.026 to 0.218±0.046; 67Ga-citrate, 0.221±0.016; 125I-HSA, 0.198±0.019], the infected muscle to blood ratio was much higher for 18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31±0.76 to 14.89±2.26; 67Ga-citrate, 1.24±0.67; 125I-HSA, 0.20±0.02). The draining reactive lymph nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I-HSA. The uptake of 3H-thymidine and l-11C- or 3H-methionine in the infected muscle was lower than that of 18F- or 3H-FDG at 2 h postinjection, 3H-thymidine = 0.039±0.005 and L-3H-methionine = 0.063±0.007 (%ID/g) x kg. Autoradiographs showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be a promising infection detection agent. (orig.)

  7. Quantitative study in vivo of methionine cycle in humans using [methyl-2H3]- and [1-13C]methionine

    International Nuclear Information System (INIS)

    Kinetic aspects of body methionine (MET) metabolism were examined in healthy young men during the fed and postabsorptive (PA) states. Rates of MET incorporation (S) into and release (B) from body proteins; transmethylation (TM); and remethylation (RM) and transsulfuration (TS) of homocysteine (HCY) were estimated with the aid of a 5-h constant intravenous infusion of [methyl-2H3]- and [1-13C]methionine. The isotopic data (plasma methionine labeling and 13C enrichment of expired air) were submitted to a stochastic model of amino acid metabolism. During the fed state, the subjects (n = 4) received, at 20-min intervals, small isonitrogenous isocaloric meals containing a complete L-amino acid mixture supplying MET at a rate equivalent to 198 mumol.kg body wt-1.day-1. The PA subjects (n = 4) received the isotope after a 10-h overnight fast. For the PA group, the components of MET metabolism were as follows: S, 20 +/- 0.5; B, 24 +/- 0.5; TM, 5.8 +/- 0.6; RM, 1.8 +/- 0.4; and TS, 4.0 +/- 0.4 (+/-SE) mumol.kg-1.h-1. During the fed state the values were S, 26 +/- 2.5; B, 18 +/- 2; TM, 14 +/- 1.3; RM, 5.7 +/- 0.9; and TS 8.3 +/- 0.6 mumol.kg-1.h-1. The meal-induced changes in B, TM, RM, and TS were significant (P less than 0.05). Comparison of the partitioning of MET between S and TM (these two pathways of MET disposal constitute the ''methionine locus'') in the PA and in the fed states indicates that the MET locus is of regulatory importance in MET homeostasis. A twofold increase in the partitioning of MET to TM was observed in the fed state. The increase in HCY recycling, relative to TS (these two pathways of HCY disposal constitute the ''HCY locus''), in the fed state did not reach statistical significance when compared with the PA state. Total daily TM are estimated to be 238 +/- 22 mumol/kg. This is similar to the estimate generated by the methyl balance model of Mudd and Poole which approximated 241 mumol/kg

  8. Biosynthesis of ethylene from methionine in aminoethoxyvinylglycine-resistant avocado tissue.

    Science.gov (United States)

    Baker, J E; Anderson, J D; Adams, D O; Apelbaum, A; Lieberman, M

    1982-01-01

    This study was conducted to determine if aminoethoxyvinylglycine (AVG) insensitivity in avocado (Persea americana Mill., Lula, Haas, and Bacon) tissue was due to an alternate pathway of ethylene biosynthesis from methionine. AVG, at 0.1 millimolar, had little or no inhibitory effect on either total ethylene production or [(14)C] ethylene production from [(14)C]methionine in avocado tissue at various stages of ripening. However, aminoxyacetic acid (AOA), which inhibits 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (the AVG-sensitive enzyme of ethylene biosynthesis), inhibited ethylene production in avocado tissue. Total ethylene production was stimulated, and [(14)C]ethylene production from [(14)C]methionine was lowered by treating avocado tissue with 1 millimolar ACC. An inhibitor of methionine adenosyltransferase (EC 2.5.1.6), l-2-amino-4-hexynoic acid (AHA), at 1.5 millimolar, effectively inhibited [(14)C]ethylene production from [(14)C]methionine in avocado tissue but had no effect on total ethylene production during a 2-hour incubation. Rates of [(14)C]AVG uptake by avocado and apple (Malus domestica Borkh., Golden Delicious) tissues were similar, and [(14)C]AVG was the only radioactive compound in alcohol-soluble fractions of the tissues. Hence, AVG-insensitivity in avocado tissue does not appear to be due to lack of uptake or to metabolism of AVG by avocado tissue. ACC synthase activity in extracts of avocado tissue was strongly inhibited (about 60%) by 10 micromolar AVG. Insensitivity of ethylene production in avocado tissue to AVG may be due to inaccessibility of ACC synthase to AVG. AVG-resistance in the avocado system is, therefore, different from that of early climacteric apple tissue, in which AVG-insensitivity of total ethylene production appears to be due to a high level of endogenous ACC relative to its rate of conversion to ethylene. However, the sensitivity of the avocado system to AOA and AHA, dilution of labeled ethylene production by ACC

  9. Realization of an apparatus for the synthesis and detection of carbon 11 labelled fatty acids and of a data acquisition system for the study of the myocardial methabolism of radiopharmaceuticals

    International Nuclear Information System (INIS)

    This thesis describes the study and the realization of an apparatus to synthesize fatty acids labelled with carbon 11, a radioactive isotope with an half-life of 20.38 minutes. A system of gamma-ray detection with data processing designed for the study of the myocardiac metabolism of radiopharmaceuticals using isolated rat hearts as experimental models. The synthesis of carbon 11 labelled fatty acids required a preliminary study of the manufacture of this isotope at the synchrocyclotron of the I.P.N. (Lyon). The method chosen is the nuclear reaction (d,xn) with naturally occurring boron trioxide as the target. The apparatus was designed so as extract carbon 11 from the target in the form of 11CO2 which can then be used in the synthesis of carbon 11 labelled hexadecanoique, heptadecanoic and beta-methyl hexadecanoic acids. The time scale of this synthesis must be compatible with the short half-like of the isotope. In order to study these compounds 'in vivo' on the experimental model of isolated rat hearts, a system of detection, which functions either in a simple gamma mode or in a gamma-gamma coincidence mode, was developed. This apparatus can attain a rate of approximately 50 000 counts/sec. per channel, thus it is possible to obtain information about rapid phases of metabolism with a satisfactory statistical precision. Moreover the spectral analysis of the gamma-ray permits the simultaneous detection of different radioisotopes. Hence it was possible to compare the behaviour of carbon 11 labelled fatty acids with homologous molecules marked with iodine 123. The analysis of the experimental results was achieved witha computer based on an I.B.M. compatible PC-XT. The essential parts of this system are a data-acquisition card for the PC, code for the acquisition and the data processing

  10. Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takeshi [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Haradahira, Terushi [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)], E-mail: terushi@niu.ac.jp; Fujimoto, Noriko [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Okauchi, Takashi; Maeda, Jun; Suzuki, Kazutoshi; Suhara, Tetsuya [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Yamamoto, Fumihiko; Sasaki, Shigeki; Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Yamaguchi, Hiroshi [Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Maeda, Minoru [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-02-15

    High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[{sup 11}C]methoxyphenyl)-2(1H)-quinolone ([{sup 11}C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-D-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[{sup 11}C]4HQ (5Et-[{sup 11}C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[{sup 11}C]4HQ (5I-[{sup 11}C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[{sup 11}C]4HQ and 5I-[{sup 11}C]4HQ was quite similar to that previously observed between [{sup 11}C]L-703,717 and [{sup 11}C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these {sup 11}C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[{sup 11}C]4HQ at 1 min after intravenous injections were comparable to that of [{sup 11}C]4HQ, but they were 1.3-2.1 times higher than that of [{sup 11}C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [{sup 11}C]4HQ and 5Et-[{sup 11}C]4HQ in contrast to [{sup 11}C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[{sup 11}C]4HQ (16-36% inhibition) but not that of 5I-[{sup 11}C]4HQ. In this study, it was found that a small structural change in [{sup 11}C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [{sup 11}C]4-hydroxyquinolones on the NMDA ion channel - agonist-sensitive and agonist-insensitive (or antagonist-preferring) sites.

  11. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions.

    Science.gov (United States)

    Afzelius, Pia; Nielsen, Ole L; Alstrup, Aage Ko; Bender, Dirk; Leifsson, Páll S; Jensen, Svend B; Schønheyder, Henrik C

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. (18)F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while (11)C-methionine and particularly (11)C-PK11195 and (68)Ga-citrate accumulated to a lesser extent in infectious foci. (18)F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions. PMID:27069765

  12. Gamma camera based FDG PET in oncology

    International Nuclear Information System (INIS)

    Positron Emission Tomography(PET) was introduced as a research tool in the 1970s and it took about 20 years before PET became an useful clinical imaging modality. In the USA, insurance coverage for PET procedures in the 1990s was the turning point, I believe, for this progress. Initially PET was used in neurology but recently more than 80% of PET procedures are in oncological applications. I firmly believe, in the 21st century, one can not manage cancer patients properly without PET and PET is very important medical imaging modality in basic and clinical sciences. PET is grouped into 2 categories; conventional (c) and gamma camera based (CB) PET. CBPET is more readily available utilizing dual-head gamma cameras and commercially available FDG to many medical centers at low cost to patients. In fact there are more CBPET in operation than cPET in the USA. CBPET is inferior to cPET in its performance but clinical studies in oncology is feasible without expensive infrastructures such as staffing, rooms and equipments. At Ajou university Hospital, CBPET was installed in late 1997 for the first time in Korea as well as in Asia and the system has been used successfully and effectively in oncological applications. Our was the fourth PET operation in Korea and I believe this may have been instrumental for other institutions got interested in clinical PET. The following is a brief description of our clinical experience of FDG CBPET in oncology

  13. Parasites in pet reptiles

    Directory of Open Access Journals (Sweden)

    Mavri Urška

    2011-05-01

    Full Text Available Abstract Exotic reptiles originating from the wild can be carriers of many different pathogens and some of them can infect humans. Reptiles imported into Slovenia from 2000 to 2005, specimens of native species taken from the wild and captive bred species were investigated. A total of 949 reptiles (55 snakes, 331 lizards and 563 turtles, belonging to 68 different species, were examined for the presence of endoparasites and ectoparasites. Twelve different groups (Nematoda (5, Trematoda (1, Acanthocephala (1, Pentastomida (1 and Protozoa (4 of endoparasites were determined in 26 (47.3% of 55 examined snakes. In snakes two different species of ectoparasites were also found. Among the tested lizards eighteen different groups (Nematoda (8, Cestoda (1, Trematoda (1, Acanthocephala (1, Pentastomida (1 and Protozoa (6 of endoparasites in 252 (76.1% of 331 examined animals were found. One Trombiculid ectoparasite was determined. In 563 of examined turtles eight different groups (Nematoda (4, Cestoda (1, Trematoda (1 and Protozoa (2 of endoparasites were determined in 498 (88.5% animals. In examined turtles three different species of ectoparasites were seen. The established prevalence of various parasites in reptiles used as pet animals indicates the need for examination on specific pathogens prior to introduction to owners.

  14. Activities of methionine-γ-lyase in the acidophilic archaeon “Ferroplasma acidarmanus” strain fer1

    Directory of Open Access Journals (Sweden)

    Khan MA

    2013-04-01

    Full Text Available M A Khan,1 Madeline M López-Muñoz,2 Charles W Kaspar,3 Kai F Hung1 1Department of Biological Sciences, Eastern Illinois University, Charleston, IL, USA; 2Department of Biology, Universidad de Puerto Rico, Mayaguez, Puerto Rico; 3Bacteriology Department, University of Wisconsin, Madison, WI, USA Abstract: Biogeochemical processes on exposed pyrite ores result in extremely high levels of sulfuric acid at these locations. Acidophiles that thrive in these conditions must overcome significant challenges, including an environment with proton concentrations at pH 3 or below. The role of sulfur metabolism in the archaeon “Ferroplasma acidarmanus” strain fer1's ability to thrive in this environment was investigated due to its growth-dependent production of methanethiol, a volatile organic sulfur compound. Two putative sequences for methionine-γ-lyase (EC 4.4.1.11, an enzyme known to carry out α, γ-elimination on L-methionine to produce methanethiol, were identified in fer1. Bioinformatic analyses identified a conserved pyridoxal-5'-phosphate (PLP binding domain and a partially conserved catalytic domain in both putative sequences. Detection of PLP-dependent and L-methionine-dependent production of α-keto compounds and thiol groups in fer1 confirmed the presence of methionine-γ-lyase activity. Further, fer1 lysate was capable of processing related substrates, including D-methionine, L-cysteine, L-cystathionine, and L/D-homocysteine. When the two putative fer1 methionine-γ-lyase gene-coded proteins were expressed in Escherichia coli cells, one sequence demonstrated an ability to carry out α, γ-elimination activity, while the other exhibited γ-replacement activity. These fer1 methionine-γ-lyases also exhibited optimum pH, substrate specificity, and catalytic preferences that are different from methionine-γ-lyases from other organisms. These differences are discussed in the context of molecular phylogeny constructed using a maximum

  15. Quantitative PET imaging with the 3T MR-BrainPET

    International Nuclear Information System (INIS)

    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner

  16. PET and PET/CT in oncology: the key of diagnostic challenge

    International Nuclear Information System (INIS)

    In this presentation authors present use of positron emission tomography (PET) in oncology. This lecture is divided to the following parts: (1) Assessment of treatment response; (2) Treatment monitoring by PET: clinical examples; (3) PET for early response assessment; (4) Use of PET in Radiotherapy planning

  17. Myasthenia gravis: 75Se-seleno-methionine scanning of thymus gland

    International Nuclear Information System (INIS)

    The 75Se-seleno-methionine isotope thymus scanning was examined in a series of patients with myasthenia gravis. The patients were given 4 μC/kg hence a total of 250-300 μC 75Se-seleno-methionine, intravenously. The method proved useful and informative in the diagnostics of myasthenia. Prior to thymectomy, the thymic tumour or a large gland could be observed and some hints could be gained for the biological activity of the gland. After the operation, the success of thymectomy could be checked and later a possible recidive could be shown or excluded. In non-operative cases the change in thymic activity could be followed which was an important sign of a malignant or tumorous growth of the thymus. (author)

  18. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Directory of Open Access Journals (Sweden)

    Rosa Castellano

    Full Text Available Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight were restrictively-fed diets providing either an adequate (CTRL or a deficient methionine supply (MD during 10 days (n=6 per group. At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently

  19. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells

    OpenAIRE

    Maddocks, Oliver D.K.; Christiaan F Labuschagne; Adams, Peter D; Vousden, Karen H.

    2016-01-01

    Summary: Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under ...

  20. Heterologous production of methionine-γ-lyase from brevibacterium linens in lactococcus lactis and formation of volatile sulfur compounds

    OpenAIRE

    Hanniffy, Sean; Philo, Mark; Peláez, Carmen; Gasson, M. J.; Requena, Teresa; Martínez-Cuesta, M. Carmen

    2009-01-01

    The conversion of methionine to volatile sulfur compounds (VSCs) is of great importance in flavor formation during cheese ripening and is the focus of biotechnological approaches toward flavor improvement. A synthetic mgl gene encoding methionine-γ-lyase (MGL) from Brevibacterium linens BL2 was cloned into a Lactococcus lactis expression plasmid under the control of the nisin-inducible promoter PnisA. When expressed in L. lactis and purified as a recombinant protein, MGL was shown to degrade ...

  1. Children's drawings and attachment to pets.

    Science.gov (United States)

    Kidd, A H; Kidd, R M

    1995-08-01

    To help confirm the concept that distances placed between the self and other figures in children's drawings represent emotional distances, 242 pet-owning and 35 nonpet-owning kindergartners through eighth graders drew pictures of themselves, a pet, and/or a family member. Owners drew pets significantly closer than family-figures although the younger the child, the greater the distance between self and pet. Older children drew themselves holding pets significantly more often, but younger children placed the family-figure between the self and the pet significantly more often. There were no significant gender differences in self-figure/pet-figure distances, but cats, dogs, caged animals, and farm animals were placed significantly closer to self-figures than were fish. Over-all, owners were clearly emotionally closer to pets than to family members, but nonowners were as close emotionally to family members as were owners. PMID:7501763

  2. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian;

    2013-01-01

    described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision......Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases...

  3. A continuous spectrophotometric assay and nonlinear kinetic analysis of methionine γ-lyase catalysis.

    Science.gov (United States)

    Foo, Timothy C; Terentis, Andrew C; Venkatachalam, Kallidaikurichi V

    2016-08-15

    In this article, we present a new, easy-to-implement assay for methionine γ-lyase (MGL)-catalyzed γ-elimination reactions of l-methionine and its analogues that produce α-ketobutyrate (α-KB) as product. The assay employs ultraviolet-visible (UV-Vis) spectrophotometry to continuously monitor the rate of formation of α-KB by its absorbance at 315 nm. We also employ a nonlinear data analysis method that obviates the need for an "initial slope" determination, which can introduce errors when the progress curves are nonlinear. The spectrophotometric assay is validated through product analysis by (1)H NMR (nuclear magnetic resonance), which showed that under the conditions of study l-methionine (l-met) and l-methionine sulfone (l-met sulfone) substrates were converted to α-KB product with greater than 99% yield. Using this assay method, we determined for the first time the Michaelis-Menten parameters for a recombinant form of MGL from Porphyromonas gingivalis, obtaining respective kcat and Km values of 328 ± 8 min(-1) and 1.2 ± 0.1 mM for l-met γ-elimination and 2048 ± 59 min(-1) and 38 ± 2 mM for l-met sulfone γ-elimination reactions. We envisage that this assay method will be useful for determining the activity of MGL γ-elimination reactions that produce α-KB as the end product. PMID:27235171

  4. Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity

    OpenAIRE

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A.; Thompson, Peter M.; Bortolato, Marco

    2014-01-01

    Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous SNP that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood posttranslation...

  5. A sulfonium cation intermediate in the mechanism of methionine sulfoxide reductase B: a DFT study.

    Science.gov (United States)

    Robinet, Jesse J; Dokainish, Hisham M; Paterson, David J; Gauld, James W

    2011-07-28

    The hybrid density functional theory method B3LYP in combination with three systematically larger active site models has been used to investigate the substrate binding and catalytic mechanism by which Neisseria gonorrhoeae methionine sulfoxide reductase B (MsrB) reduces methionine-R-sulfoxide (Met-R-SO) to methionine. The first step in the overall mechanism is nucleophilic attack of an active site thiolate at the sulfur of Met-R-SO to form an enzyme-substrate sulfurane. This occurs with concomitant proton transfer from an active site histidine (His480) residue to the substrates oxygen center. The barrier for this step, calculated using our largest most complete active site model, is 17.2 kJ mol(-1). A subsequent conformational rearrangement and intramolecular -OH transfer to form an enzyme-derived sulfenic acid ((Cys495)S-OH) is not enzymatically feasible. Instead, transfer of a second proton from a second histidyl active site residue (His477) to the sulfurane's oxygen center to give water and a sulfonium cation intermediate is found to be greatly preferred, occurring with a quite low barrier of just 1.2 kJ mol(-1). Formation of the final product complex in which an intraprotein disulfide bond is formed with generation of methionine preferably occurs in one step via nucleophilic attack of the sulfur of a second enzyme thiolate ((Cys440)S(-)) at the S(Cys495) center of the sulfonium intermediate with a barrier of 23.8 kJ mol(-1). An alternate pathway for formation of the products via a sulfenic acid intermediate involves enzymatically feasible, but higher energy barriers. The role and impact of hydrogen bonding and active site residues on the properties and stability of substrate and mechanism intermediates and the affects of mutating His477 are also examined and discussed. PMID:21721538

  6. Structure-Functional Study of Tyrosine and Methionine Dipeptides: An Approach to Antioxidant Activity Prediction

    OpenAIRE

    Anna Torkova; Olga Koroleva; Ekaterina Khrameeva; Tatyana Fedorova; Mikhail Tsentalovich

    2015-01-01

    Quantum chemical methods allow screening and prediction of peptide antioxidant activity on the basis of known experimental data. It can be used to design the selective proteolysis of protein sources in order to obtain products with antioxidant activity. Molecular geometry and electronic descriptors of redox-active amino acids, as well as tyrosine and methionine-containing dipeptides, were studied by Density Functional Theory method. The calculated data was used to reveal several descriptors r...

  7. Estimates of methionine and sulfur amino acid requirements for laying hens using different models

    OpenAIRE

    AA Saki; R Naseri Harsini; MM Tabatabaei; Zamani, P.; M Haghight

    2012-01-01

    This experiment was conducted to evaluate the effects of dietary methionine (Met) content on the performance of white commercial laying hens and to determine Met and total sulfur amino acids requirements (TSAA). These requirements were estimated using three statistical models (broken-line regression, exponential and second order equations) to evaluate their abilit to determine amino acid requirements. A total of 216 laying hens (23 wks of age) was used in a completely randomized design (CRD) ...

  8. Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine

    Czech Academy of Sciences Publication Activity Database

    Pícha, Jan; Liboska, Radek; Buděšínský, Miloš; Jiráček, Jiří; Pawelczak, M.; Mucha, A.

    2011-01-01

    Roč. 26, č. 2 (2011), s. 155-161. ISSN 1475-6366 R&D Projects: GA ČR GA203/06/1405; GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : aminophosphonates * aminophospinates * methionine * norleucine * phosphorus containing dipeptides * cytosolic leucine aminopeptidase * inhibitors Subject RIV: CC - Organic Chemistry Impact factor: 1.617, year: 2011

  9. Role of β-adrenergic receptors in the hyperphagic and hypermetabolic responses to dietary methionine restriction

    OpenAIRE

    Plaisance, Eric P; Henagan, Tara M.; Echlin, Haley; Boudreau, Anik; Hill, Kasey L.; Lenard, Natalie R.; Hasek, Barbara E.; Orentreich, Norman; Gettys, Thomas W

    2010-01-01

    Dietary methionine restriction (MR) limits fat deposition and decreases plasma leptin, while increasing food consumption, total energy expenditure (EE), plasma adiponectin, and expression of uncoupling protein 1 (UCP1) in brown and white adipose tissue (BAT and WAT). β-adrenergic receptors (β-AR) serve as conduits for sympathetic input to adipose tissue, but their role in mediating the effects of MR on energy homeostasis is unclear. Energy intake, weight, and adiposity were modestly higher in...

  10. The Pathogenesis of Ethanol versus Methionine and Choline Deficient Diet-Induced Liver Injury

    OpenAIRE

    Gyamfi, Maxwell Afari; Damjanov, Ivan; French, Samuel; Wan, Yu-Jui Yvonne

    2007-01-01

    The differences and similarities of the pathogenesis of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) were examined. Mice (6/group) received 1 of 4 Lieber-Decarli liquid diets for 6 weeks: (1) paired-fed control diet; (2) control diet with ethanol (ethanol); (3) paired-fed methionine/choline deficient (MCD) diet; and (4) MCD plus ethanol (combination). Hepatotoxicity, histology, and gene expression changes were examined. Both MCD and ethanol induced macrovesicular steatosis. Howeve...

  11. Acute liver injury induces nucleocytoplasmic redistribution of hepatic methionine metabolism enzymes

    OpenAIRE

    Delgado, Miguel; Garrido, Francisco; Pérez-Miguelsanz, Juliana; Pacheco, María; Partearroyo, Teresa; Pérez-Sala, Dolores; Pajares, María A.

    2014-01-01

    Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities,...

  12. Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity

    OpenAIRE

    Wesam Elremaly; Ibrahim Mohamed; Thérèse Rouleau; Jean-Claude Lavoie

    2016-01-01

    Background: The oxidation of the methionine adenosyltransferase (MAT) by the combined impact of peroxides contaminating parenteral nutrition (PN) and oxidized redox potential of glutathione is suspected to explain its inhibition observed in animals. A modification of MAT activity is suspected to be at origin of the PN-associated liver disease as observed in newborns. We hypothesized that the correction of redox potential of glutathione by adding glutathione in PN protects the MAT activity. ...

  13. Synthesis and PET studies of [11C-cyano]letrozole (Femara), an aromatase inhibitor drug

    International Nuclear Information System (INIS)

    Introduction: Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (Ki=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [11C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [11C-cyano]letrozole fraction in arterial plasma were also measured. Results: [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. Conclusion: [11C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as

  14. Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate.

    Science.gov (United States)

    Krivokapich, J; Huang, S C; Schelbert, H R

    1993-06-01

    The dual purposes of this study with positron emission tomography were to measure the effects of dobutamine on myocardial blood flow and oxidative metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13) ammonia in quantitating flow in normal subjects. Flow was quantitated with N-13 ammonia at rest and at peak dobutamine infusion (40 micrograms/kg/min) in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at rest and peak dobutamine infusion using the clearance rate of C-11 acetate, k mono (min-1). A 2-compartment kinetic model was applied to the early phase of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure products were 7,318 +/- 1,102 and 19,937 +/- 3,964 beats/min/mm Hg, respectively, and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77 +/- 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer. Rest and dobutamine flows estimated with C-11 acetate were highly correlated with those determined with N-13 ammonia (r = 0.92). k mono increased from 0.05 +/- 0.01 to 0.18 +/- 0.02 min-1, and correlated highly with the increase in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase in cardiac demand associated with dobutamine is highly correlated with an increase in supply and oxidative metabolism. C-11 acetate is a unique tracer that can be used to image both flow and metabolism simultaneously. PMID:8498380

  15. The potential of carbon-11 and fluorine-18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

    International Nuclear Information System (INIS)

    The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is up-regulated in the brain of subjects suffering from neuro-degenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to micro-glia activation making thus the TSPO a marker of choice of neuro-inflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980's with the preparation of the 3-iso-quinolinecarboxamide [11C]PK11195. To date, an impressive number of promising compounds - [11C]PK11195-challengers - have been developed; some radioligands - for example, [11C]PBR28, [11C]DPA-713, [18F]FEDAA1106 and [18F]DPA-714 - are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [11C]methylations using [11C]MeI or [11C]MeOTf and SN2- type nucleophilic aliphatic [18F]fluorinations - two processes illustrating the state-of-the-art arsenal of reactions that involves these two short-lived radioisotopes - but alternative processes, such as [11C]carbonylations using [11C]CO and [11C]COCl2 as well as SNAr-type nucleophilic [18F]fluorinations, have also been reported and as such, reviewed herein. (authors)

  16. Role of Ginkgo Biloba in Hyperhomocysteinemia Induced in Rats By L-Methionine and Gamma Irradiation

    International Nuclear Information System (INIS)

    The objective of this study is to evaluate the role of Ginkgo biloba in hyperhomocysteinemia and oxidative stress. Methionine was supplied orally to adult male albino rats with a dose of 1.7 g/kg/day during 4 weeks. Irradiation was applied to rats by whole body gamma irradiation with a dose of 2 Gy/week up to a total dose of 8 Gy. Ginkgo biloba (100 mg/kg/day) was supplemented orally to rats, daily, during the period of methionine administration and/or radiation exposure. Biochemical analysis in blood and brain tissues showed that methionine and/or gamma irradiation produced significant increases in homocysteine and acetylcholine esterase levels and significant decrease in nitric oxide (NO). Significant increase in malondialdehyde (MDA) with significant decreases in glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase levels were observed and alteration in plasma lipid profile was also recorded. Ginkgo biloba supplementation has significantly decreased homocysteine and acetylcholine esterase levels and increased NO while was associated with significant improvement of oxidative stress and lipid profile. It could be concluded that the protective effect of Gingko biloba against hyperhomocysteinemia and oxidative stress is attributed to its antioxidant and free radicals scavenging properties.

  17. Proton Therapy Verification with PET Imaging

    OpenAIRE

    Zhu, Xuping; Fakhri, Georges El

    2013-01-01

    Proton therapy is very sensitive to uncertainties introduced during treatment planning and dose delivery. PET imaging of proton induced positron emitter distributions is the only practical approach for in vivo, in situ verification of proton therapy. This article reviews the current status of proton therapy verification with PET imaging. The different data detecting systems (in-beam, in-room and off-line PET), calculation methods for the prediction of proton induced PET activity distributions...

  18. The rise and fall of PET and PET/CT. A German perspective

    International Nuclear Information System (INIS)

    PET is being considered a diagnostic commodity in clinical practice worldwide and thus receives increasing attention by health insurances and governmental organizations. In Germany, however, neither PET nor PET/CT are subject to reimbursement. This renders clinical PET and PET/CT imaging a challenge both in general hospital environment and in private practice. This article describes briefly these challenges, which are not solely related to turf battles and associated costs. (orig.)

  19. Kinetic modeling in PET imaging of hypoxia

    DEFF Research Database (Denmark)

    Li, Fan; Jørgensen, Jesper Tranekjær; Hansen, Anders E;

    2014-01-01

    used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET...

  20. Pet care during preadolescence: developmental considerations.

    Science.gov (United States)

    Davis, J H

    1987-01-01

    This exploratory study investigated pet care in relation to psychosocial development during preadolescence. A group of male and female preadolescents (n = 22) at appropriate grade level for age completed a dog care responsibility inventory. The results revealed that preadolescents in general do not routinely care for pets. Mothers appear to assume most pet care tasks. PMID:3664972

  1. Saying Goodbye: Pet Loss and Its Implications

    Science.gov (United States)

    Duffey, Thelma

    2005-01-01

    Pets can be loyal, loving, and entertaining members of a family. Their deaths are generally experienced as painful losses by the people who love them, even though the grief experience is often culturally disenfranchised. In this manuscript, we discuss the role that pets can play in a person's life; the effects that pet loss can have on the people…

  2. 36 CFR 13.1234 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  3. PET and SPECT in neurology

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium). Dept. of Radiology and Nuclear Medicine; Vries, Erik F.J. de; Waarde, Aren van [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Otte, Andreas (ed.) [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology

    2014-07-01

    PET and SPECT in Neurology highlights the combined expertise of renowned authors whose dedication to the investigation of neurological disorders through nuclear medicine technology has achieved international recognition. Classical neurodegenerative disorders are discussed as well as cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders, and inflammatory and infectious diseases of the CNS. The latest results in nuclear brain imaging are detailed. Most chapters are written jointly by a clinical neurologist and a nuclear medicine specialist to ensure a multidisciplinary approach. This state-of-the-art compendium will be valuable to anybody in the field of neuroscience, from the neurologist and the radiologist/nuclear medicine specialist to the interested general practitioner and geriatrician. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences, the other volumes covering PET and SPECT in psychiatry and in neurobiological systems.

  4. Understanding advertising in pet nutrition.

    Science.gov (United States)

    Brown, R G

    1994-04-01

    Advertising is part of the effort to attract attention of consumers to products, in this case, pet foods. It is generally benign in its effect, but it can be misleading, although rarely deliberately so. It uses a specialized vocabulary, which must be mastered if one is to understand what is intended. For all of the expense and effort, advertising figures directly in relatively few decisions to purchase. Its main intention is to call our attention to a particular pet food and to give that product an image. If the pet food does not perform in the consumer's hands, then all of the advertising on earth will not be persuasive. On the other hand, if a product performs well, the word-of-mouth will be positive and that mode of advertising is one of the most effective. PMID:8076285

  5. Promoting the exotic pet practice.

    Science.gov (United States)

    Harris, Don J

    2005-09-01

    The marketing and promotion of an exotic pet veterinary practice allows the use of strategies that are not necessarily available in other veterinary disciplines. The advantage that an exotics practice enjoys is that it is able to capitalize not only on the unique nature of the species being attended but also on the specialized features of the hospital itself that make it specifically appropriate in caring for exotic pets. Before marketing, however, comes the responsibility that the practice live up to the claims made in promotional materials. A practice cannot ethically be presented as an "exotics" practice if it is nothing more than a dog and cat facility that is willing to attend to exotic pets. It is the competence of the veterinary staff and the appropriateness of the facility that determines the suitability of the practice for exotics management. PMID:16129354

  6. PET and SPECT in neurology

    International Nuclear Information System (INIS)

    PET and SPECT in Neurology highlights the combined expertise of renowned authors whose dedication to the investigation of neurological disorders through nuclear medicine technology has achieved international recognition. Classical neurodegenerative disorders are discussed as well as cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders, and inflammatory and infectious diseases of the CNS. The latest results in nuclear brain imaging are detailed. Most chapters are written jointly by a clinical neurologist and a nuclear medicine specialist to ensure a multidisciplinary approach. This state-of-the-art compendium will be valuable to anybody in the field of neuroscience, from the neurologist and the radiologist/nuclear medicine specialist to the interested general practitioner and geriatrician. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences, the other volumes covering PET and SPECT in psychiatry and in neurobiological systems.

  7. Oxidative stress inactivates cobalamin-independent methionine synthase (MetE in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elise R Hondorp

    2004-11-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

  8. Oxidative Stress Inactivates Cobalamin-Independent Methionine Synthase (MetE in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Hondorp Elise R

    2004-01-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

  9. Understanding advertising in pet nutrition.

    OpenAIRE

    Brown, R G

    1994-01-01

    Advertising is part of the effort to attract attention of consumers to products, in this case, pet foods. It is generally benign in its effect, but it can be misleading, although rarely deliberately so. It uses a specialized vocabulary, which must be mastered if one is to understand what is intended. For all of the expense and effort, advertising figures directly in relatively few decisions to purchase. Its main intention is to call our attention to a particular pet food and to give that prod...

  10. Evaluation of [11C]RTI-121 as a selective radioligand for PET studies of the dopamine transporter

    International Nuclear Information System (INIS)

    The cocaine analogue RTI-121 (3β-(4-iodophenyl)tropane-2β-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [11C]RTI-55 (2↔-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site. The results indicate that [11C]RTI-121 could be used in preference to [11C]RTI-55 in man. Experimentally, [11C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography

  11. The Petit Rat (pet/pet), a New Semilethal Mutant Dwarf Rat with Thymic and Testicular Anomalies

    OpenAIRE

    Chiba, Junko; Suzuki, Katsushi; Suzuki, Hiroetsu

    2008-01-01

    The petit rat (pet/pet) is a recently discovered semilethal mutant dwarf. The neonatal pet/pet rats had a low body weight and small thymus and testis. During the first 3 d after birth, 50% of the male and 80% of the female pet/pet pups were lost or found dead. Surviving pet/pet rats showed marked retardation of postnatal growth, and their body weights were 41% (female rats) and 32% (male rats) of those of normal rats at the adult stage. The pet/pet rats exhibited proportional dwarfism, and th...

  12. Competitive advantage of PET/MRI

    International Nuclear Information System (INIS)

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved

  13. PET and PET/CT in malignant melanoma

    International Nuclear Information System (INIS)

    The advantages that it has the PET/CT are: 1. It diminishes mainly positive false lesions. It identifies physiologic accumulate places. 2. It diminishes in smaller grade false negative. Small injuries. Injuries with low grade concentration. Injure on intense activity areas. 3. Precise anatomical localization of accumulate places. 4. Reduction of the acquisition time. (Author)

  14. Hybrid MR-PET in Neuroimaging.

    Science.gov (United States)

    Bisdas, S; Lá Fougere, C; Ernemann, U

    2015-10-01

    Hybrid magnetic resonance (MR)-positron emission tomography (MR-PET) is a novel technology with advantages over sequential MR and PET imaging, allowing maintain full individual diagnostic performance with negligible mutual interference between the two hardware settings. Obvious synergies between MR and PET in acquisition of anatomical, functional, and molecular information for neurological diseases into one single image pave the way for establishing clear clinical indications for hybrid MR-PET as well as addressing unmet neuroimaging needs in future clinics and research. Further developments in attenuation correction, quantification, workflow, and effective MR-PET data management might unfold the full potential of integrated multimodality imaging. PMID:26227618

  15. FDG-PET response-adapted therapy

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2014-01-01

    Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Early determination of treatment sensitivity by FDG-PET is the best tool to guide individualized......, response-adapted treatment. Several ongoing or recently completed trials have investigated the use of FDG-PET/CT for early response-adapted HL therapy. The results are encouraging, but the data are immature, and PET response-adapted HL therapy is discouraged outside the setting of clinical trials. PET...

  16. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Ho; Choi, Yong, E-mail: ychoi.image@gmail.com; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun [Department of Electronic Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742 (Korea, Republic of); Oh, Chang Hyun; Park, Hyun-wook [Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Kim, Kyung Min; Kim, Jong Guk [Korea Institute of Radiological and Medical Science, 75 Nowon-ro, Nowon-gu, Seoul 139-709 (Korea, Republic of)

    2015-05-15

    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was

  17. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was

  18. PET and SPET tracers for mapping the cardiac nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, 17176 Stockholm (Sweden)

    2002-03-01

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[{sup 18}F]fluorodopamine, (-)-6-[{sup 18}F]fluoronorepinephrine and (-)-[{sup 11}C]epinephrine, and radiolabelled catecholamine analogues, such as [{sup 123}I]meta-iodobenzylguanidine, [{sup 11}C]meta-hydroxyephedrine, [{sup 18}F]fluorometaraminol, [{sup 11}C]phenylephrine and meta-[{sup 76}Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[{sup 18}F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility

  19. PET and SPET tracers for mapping the cardiac nervous system

    International Nuclear Information System (INIS)

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[18F]fluorodopamine, (-)-6-[18F]fluoronorepinephrine and (-)-[11C]epinephrine, and radiolabelled catecholamine analogues, such as [123I]meta-iodobenzylguanidine, [11C]meta-hydroxyephedrine, [18F]fluorometaraminol, [11C]phenylephrine and meta-[76Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[18F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging. (orig.)

  20. The MiniPET: a didactic PET system

    Science.gov (United States)

    Pedro, R.; Silva, J.; Gurriana, L.; Silva, J. M.; Maio, A.; Soares Augusto, J.

    2013-03-01

    The MiniPET project aims to design and build a small PET system. It consists of two 4 × 4 matrices of 16 LYSO scintillator crystals and two PMTs with 16 channels resulting in a low cost system with the essential functionality of a clinical PET instrument. It is designed to illustrate the physics of the PET technique and to provide a didactic platform for the training of students and nuclear imaging professionals as well as for scientific outreach. The PET modules can be configured to test for the coincidence of 511 keV gamma rays. The model has a flexible mechanical setup [1] and can simulate 14 diferent ring geometries, from a configuration with as few as 18 detectors per ring (ring radius phi=51 mm), up to a geometry with 70 detectors per ring (phi=200 mm). A second version of the electronic system [2] allowed measurement and recording of the energy deposited in 4 detector channels by photons from a 137Cs radioactive source and by photons resulting of the annihilation of positrons from a 22Na radioactive source. These energy spectra are used for detector performance studies, as well as angular dependency studies. In this paper, the mechanical setup, the front-end high-speed analog electronics, the digital acquisition and control electronics implemented in a FPGA, as well as the data-transfer interface between the FPGA board and a host PC are described. Recent preliminary results obtained with the 4 active channels in the prototype are also presented.

  1. The MiniPET: a didactic PET system

    International Nuclear Information System (INIS)

    The MiniPET project aims to design and build a small PET system. It consists of two 4 × 4 matrices of 16 LYSO scintillator crystals and two PMTs with 16 channels resulting in a low cost system with the essential functionality of a clinical PET instrument. It is designed to illustrate the physics of the PET technique and to provide a didactic platform for the training of students and nuclear imaging professionals as well as for scientific outreach. The PET modules can be configured to test for the coincidence of 511 keV gamma rays. The model has a flexible mechanical setup [1] and can simulate 14 diferent ring geometries, from a configuration with as few as 18 detectors per ring (ring radius φ=51 mm), up to a geometry with 70 detectors per ring (φ=200 mm). A second version of the electronic system [2] allowed measurement and recording of the energy deposited in 4 detector channels by photons from a 137Cs radioactive source and by photons resulting of the annihilation of positrons from a 22Na radioactive source. These energy spectra are used for detector performance studies, as well as angular dependency studies. In this paper, the mechanical setup, the front-end high-speed analog electronics, the digital acquisition and control electronics implemented in a FPGA, as well as the data-transfer interface between the FPGA board and a host PC are described. Recent preliminary results obtained with the 4 active channels in the prototype are also presented.

  2. Non-HPLC methods for the production of 18F, 11C and 68Ga PET tracers

    International Nuclear Information System (INIS)

    Full text: The most popular PET radionuclides in routine clinical use are 11C and 18F, although other radionuclides, such as 68Ga, continue to make headlines. This is due to their well established chemistry, their utility for labeling low molecular weight compounds, and their ease of production in modern PET cyclotrons or via commercially available generators. Their relatively short half lives, along with the global trend toward Good Manufacturing Practice in PET drug production has necessitated the development of aseptic, robust and rapid labeling methodologies. This is achieved by the use of automated radiochemistry systems, which, in turn, has allowed radiosynthesis scale-up and multiple dose preparation. Major impediments to routine production of a number of useful 11C, 18F and 68Ga PET tracers, and to new tracer development, remain: 1) the necessity of thorough system clean up in between consecutive runs; and 2) inconsistent yields and prolonged synthesis time when using HPLC methods for final product separation and purification. To address these issues, new radiochemistry applications have been developed for the radiochemistry modules: a) for 18F: FLT Lite, F-MISO Lite, F-Choline Lite, and FET Lite; b) for 11C: Acetate, Methyl Iodide, Methionine, Choline; c) for 68Ga: DOTA-Peptides. These methods utilize sterile disposable kits, and allow for the PET tracers to be purified and isolated with SPE cartridges only, thus eliminating the need for HPLC separation. The processes and the radiochemical yields obtained with these methods will be presented, and their utility discussed

  3. Principles of PET/MR Imaging.

    Science.gov (United States)

    Disselhorst, Jonathan A; Bezrukov, Ilja; Kolb, Armin; Parl, Christoph; Pichler, Bernd J

    2014-05-12

    Hybrid PET/MR systems have rapidly progressed from the prototype stage to systems that are increasingly being used in the clinics. This review provides an overview of developments in hybrid PET/MR systems and summarizes the current state of the art in PET/MR instrumentation, correction techniques, and data analysis. The strong magnetic field requires considerable changes in the manner by which PET images are acquired and has led, among others, to the development of new PET detectors, such as silicon photomultipliers. During more than a decade of active PET/MR development, several system designs have been described. The technical background of combined PET/MR systems is explained and related challenges are discussed. The necessity for PET attenuation correction required new methods based on MR data. Therefore, an overview of recent developments in this field is provided. Furthermore, MR-based motion correction techniques for PET are discussed, as integrated PET/MR systems provide a platform for measuring motion with high temporal resolution without additional instrumentation. The MR component in PET/MR systems can provide functional information about disease processes or brain function alongside anatomic images. Against this background, we point out new opportunities for data analysis in this new field of multimodal molecular imaging. PMID:24819419

  4. An introduction to PET/CT imaging

    International Nuclear Information System (INIS)

    Since its introduction in 1998, dual-modality PET/CT imaging has received great attention in the medical community. Patients are examined with both CT and PET in a whole-body single examination in the same scanner and fusion can be obtained directly obviating the need for software registration. The CT images are used for anatomic reference of the tracer uptake patterns imaged in PET, as well as for attenuation correction of the PET data. This review discusses the technical background of PET with F-18-fluorodeoxyglucose, CT and combined PET/CT devices. Clinical applications in oncology are considered. Fusion of the anatomic information provided by CT and the metabolic information provided by PET in PET/CT imaging allows a higher diagnostic accuracy for lesion localisation than PET plus CT performed independently. Image artefacts can result from CT-based attenuation methodology that can overcorrect dense objects generating hot spot artefacts in attenuation correction PET images and mismatches in CT and PET studies due to respiratory movements and the different patient positioning between both examinations. (author)

  5. Quantitative simultaneous PET-MR imaging

    Science.gov (United States)

    Ouyang, Jinsong; Petibon, Yoann; Huang, Chuan; Reese, Timothy G.; Kolnick, Aleksandra L.; El Fakhri, Georges

    2014-06-01

    Whole-body PET is currently limited by the degradation due to patient motion. Respiratory motion degrades imaging studies of the abdomen. Similarly, both respiratory and cardiac motions significantly hamper the assessment of myocardial ischemia and/or metabolism in perfusion and viability cardiac PET studies. Based on simultaneous PET-MR, we have developed robust and accurate MRI methods allowing the tracking and measurement of both respiratory and cardiac motions during abdominal or cardiac studies. Our list-mode iterative PET reconstruction framework incorporates the measured motion fields into PET emission system matrix as well as the time-dependent PET attenuation map and the position dependent point spread function. Our method significantly enhances the PET image quality as compared to conventional methods.

  6. Diseases Transmitted by Less Common House Pets.

    Science.gov (United States)

    Chomel, Bruno B

    2015-12-01

    Beside dogs and cats, the most common pets worldwide, an increasing number of pocket pets and exotic pets are making their way to more and more households, especially in North America and Europe. Although many of these animals make appropriate pets, they also can be a source of many zoonotic diseases, especially in young children and immunocompromised individuals. Some of these diseases can be life threatening, such as rabies, rat bite fever, and plague. Some others are quite common, because of the frequency of the pathogens harbored by these species, such as salmonellosis in reptiles and amphibians. Appropriate knowledge of the zoonotic agents carried by these "new" pet species is strongly recommended prior to acquiring pocket or exotic pets. Furthermore, adopting wildlife as pets is strongly discouraged, because it is always a risky action that can lead to major health issues. PMID:27337276

  7. Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry

    Science.gov (United States)

    Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

    2016-01-01

    We report a reaction apparatus developed to monitor singlet oxygen (1O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. 1O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. 1O2 concentrations in solution were linearly related to the emission intensities of airborne 1O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an 1O2 trapping agent. Products from 1O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of 1O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. 1O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with 1O2, evolution of methionine oxidation pathways at different ionization states and in different media is described.

  8. Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry.

    Science.gov (United States)

    Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

    2016-01-01

    We report a reaction apparatus developed to monitor singlet oxygen ((1)O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. (1)O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. (1)O2 concentrations in solution were linearly related to the emission intensities of airborne (1)O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an (1)O2 trapping agent. Products from (1)O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of (1)O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. (1)O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with (1)O2, evolution of methionine oxidation pathways at different ionization states and in different media is described. PMID:26306590

  9. Diagnostic imaging of exotic pets

    International Nuclear Information System (INIS)

    Radiographic, ultrasonographic, and computed tomographic (CT) imaging are important diagnostic modalities in exotic pets. The use of appropriate radiographic equipment, film-screen combinations, and radiographic projections enhances the information obtained from radiographs. Both normal findings and common radiographic abnormalities are discussed. The use of ultrasonography and CT scanning for exotic small mammals and reptiles is described

  10. PET and SPECT in psychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium); Otte, Andreas [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology; Vries, Erik F.J. de; Waarde, Aren van (eds.) [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging

    2014-09-01

    Covers classical psychiatric disorders as well as other subjects such as suicide, sleep, eating disorders, and autism. Emphasis on a multidisciplinary approach. Written by internationally acclaimed experts. PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects - such as suicide, sleep, eating disorders, and autism - are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems.

  11. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O.B.; Lassen, N.A.

    1997-01-01

    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  12. PET and SPECT in psychiatry

    International Nuclear Information System (INIS)

    Covers classical psychiatric disorders as well as other subjects such as suicide, sleep, eating disorders, and autism. Emphasis on a multidisciplinary approach. Written by internationally acclaimed experts. PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects - such as suicide, sleep, eating disorders, and autism - are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems.

  13. S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine 9 to methionine mutation on histone H3.

    Science.gov (United States)

    Jayaram, Hariharan; Hoelper, Dominik; Jain, Siddhant U; Cantone, Nico; Lundgren, Stefan M; Poy, Florence; Allis, C David; Cummings, Richard; Bellon, Steven; Lewis, Peter W

    2016-05-31

    Lysine to methionine (K-to-M) mutations in genes encoding histone H3 are thought to drive a subset of pediatric brain and bone cancers. These high-frequency K-to-M mutations occur at sites of methylation on histone H3, and tumors containing the mutant histones exhibit a global loss of specific histone methylation marks. Previous studies showed that K-to-M mutant histones, also known as oncohistones, are potent orthosteric inhibitors of specific Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain methyltransferases. However, the biochemical and biophysical details of the interaction between K-to-M mutant histones and the respective SET domain methyltransferases are currently unknown. Here, we use the histone H3K9-directed methyltransferase G9a as a model to explore the mechanism of inhibition by K-to-M oncohistones. X-ray cocrystal structures revealed that the K9M residue of histone H3 occupies the active site cavity of G9a, and kinetic analysis indicates competitive inhibition of G9a by histone H3K9M. Additionally, we find that the cofactor S-adenosyl methionine (SAM) is necessary for stable interaction between G9a and H3K9M histone. Consistent with the formation of a ternary complex, we find that the inhibitory peptide is uncompetitive with regard to SAM. These data and others indicate that K-to-M oncohistones promote global loss of specific lysine methylation through sequestration and inhibition of SAM-bound SET domain methyltransferases. PMID:27185940

  14. Temporal study of acetaminophen (APAP) and S-adenosyl-L-methionine (SAMe) effects on subcellular hepatic SAMe levels and methionine adenosyltransferase (MAT) expression and activity

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) is the leading cause of drug induced liver failure in the United States. Previous studies in our laboratory have shown that S-adenosyl methionine (SAMe) is protective for APAP hepatic toxicity. SAMe is critical for glutathione synthesis and transmethylation of nucleic acids, proteins and phospholipids which would facilitate recovery from APAP toxicity. SAMe is synthesized in cells through the action of methionine adenosyltransferase (MAT). This study tested the hypothesis that total hepatic and subcellular SAMe levels are decreased by APAP toxicity. Studies further examined MAT expression and activity in response to APAP toxicity. Male C57BL/6 mice (16-22 g) were treated with vehicle (Veh; water 15 ml/kg ip injections), 250 mg/kg APAP (15 ml/kg, ip), SAMe (1.25 mmol/kg) or SAMe administered 1 h after APAP injection (SAMe and SAMe + APAP). Hepatic tissue was collected 2, 4, and 6 h after APAP administration. Levels of SAMe and its metabolite S-adenosylhomocysteine (SAH) were determined by HPLC analysis. MAT expression was examined by Western blot. MAT activity was determined by fluorescence assay. Total liver SAMe levels were depressed at 4 h by APAP overdose, but not at 2 or 6 h. APAP depressed mitochondrial SAMe levels at 4 and 6 h relative to the Veh group. In the nucleus, levels of SAMe were depressed below detectable limits 4 h following APAP administration. SAMe administration following APAP (SAMe + APAP) prevented APAP associated decline in mitochondrial and nuclear SAMe levels. In conclusion, the maintenance of SAMe may provide benefit in preventing damage associated with APAP toxicity.

  15. Comparative PET/CT study with 11C-MET and 18F-FDG for diagnosing Glioma

    International Nuclear Information System (INIS)

    In this paper, we investigate the diagnostic value of 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) for brain gliomas, and compare the results to 18F-fluorodeoxyglucose. Forty-four patients with suspected gliomas were examined with 11C-MET and 18F-FDG PET/CT. 18F-FDG and 11C-MET PET/CT images were compared and evaluated by visual and semiquantitative analysis. The accuracy of 11C-MET and 18F-FDG PET/CT for detecting gliomas were 88.6% and 65.9%, respectively. Semiquantitative analysis showed that the 26 gliomas had higher mean ± SD T/NGmax ratio on 11C-MET PET/CT than on 18F-FDG PET/CT(1.95±0.52 vs. 0.90±0.27, t=9.101, P11C-MET had a higher sensitivity than 18F-FDG (83.3% vs.33.3%, χ2 =4.16, P18F-FDG in the sensitivity for high-grade gliomas(100% vs. 64.3%, χ2=3.20, P>0.05). The difference was no significant, too, between high-and low-grade gliomas, compared by 11C-MET T/NGmax ratio (2.07±0.51 vs. 1.81±0.52, t=1.302, P=0.205). 18F-FDG T/NGmax ratio in high-grade gliomas was significantly higher than that in low-grade gliomas (1.03±0.30 vs. 0.75±0.11, t=3.198, P=0.004). It is concluded that 11C-MET PET/CT is more accurate than 18F-FDG PET/CT for detecting and delineating gliomas, especially for low-grade gliomas, and it can play a complement role to 18F-FDG in tumor grading. (authors)

  16. Current status and future perspective of PET

    International Nuclear Information System (INIS)

    Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) detecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had, 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3

  17. In vitro selenium accessibility in pet foods is affected by diet composition and type.

    Science.gov (United States)

    van Zelst, Mariëlle; Hesta, Myriam; Alexander, Lucille G; Gray, Kerry; Bosch, Guido; Hendriks, Wouter H; Du Laing, Gijs; De Meulenaer, Bruno; Goethals, Klara; Janssens, Geert P J

    2015-06-28

    Se bioavailability in commercial pet foods has been shown to be highly variable. The aim of the present study was to identify dietary factors associated with in vitro accessibility of Se (Se Aiv) in pet foods. Se Aiv is defined as the percentage of Se from the diet that is potentially available for absorption after in vitro digestion. Sixty-two diets (dog, n 52; cat, n 10) were in vitro enzymatically digested: fifty-four of them were commercially available (kibble, n 20; pellet, n 8; canned, n 17; raw meat, n 6; steamed meat, n 3) and eight were unprocessed (kibble, n 4; canned, n 4) from the same batch as the corresponding processed diets. The present investigation examined if Se Aiv was affected by diet type, dietary protein, methionine, cysteine, lysine and Se content, DM, organic matter and crude protein (CP) digestibility. Se Aiv differed significantly among diet types (Pextrusion (n 4) revealed no effect on Se Aiv (P =0·297). These differences in Se Aiv between diet types warrant quantification of diet type effects on in vivo Se bioavailability. PMID:25994047

  18. Isotope specific resolution recovery image reconstruction in high resolution PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kotasidis, Fotis A. [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva, Switzerland and Wolfson Molecular Imaging Centre, MAHSC, University of Manchester, M20 3LJ, Manchester (United Kingdom); Angelis, Georgios I. [Faculty of Health Sciences, Brain and Mind Research Institute, University of Sydney, NSW 2006, Sydney (Australia); Anton-Rodriguez, Jose; Matthews, Julian C. [Wolfson Molecular Imaging Centre, MAHSC, University of Manchester, Manchester M20 3LJ (United Kingdom); Reader, Andrew J. [Montreal Neurological Institute, McGill University, Montreal QC H3A 2B4, Canada and Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King' s College London, St. Thomas’ Hospital, London SE1 7EH (United Kingdom); Zaidi, Habib [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Geneva Neuroscience Centre, Geneva University, CH-1205 Geneva (Switzerland); Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, PO Box 30 001, Groningen 9700 RB (Netherlands)

    2014-05-15

    Purpose: Measuring and incorporating a scanner-specific point spread function (PSF) within image reconstruction has been shown to improve spatial resolution in PET. However, due to the short half-life of clinically used isotopes, other long-lived isotopes not used in clinical practice are used to perform the PSF measurements. As such, non-optimal PSF models that do not correspond to those needed for the data to be reconstructed are used within resolution modeling (RM) image reconstruction, usually underestimating the true PSF owing to the difference in positron range. In high resolution brain and preclinical imaging, this effect is of particular importance since the PSFs become more positron range limited and isotope-specific PSFs can help maximize the performance benefit from using resolution recovery image reconstruction algorithms. Methods: In this work, the authors used a printing technique to simultaneously measure multiple point sources on the High Resolution Research Tomograph (HRRT), and the authors demonstrated the feasibility of deriving isotope-dependent system matrices from fluorine-18 and carbon-11 point sources. Furthermore, the authors evaluated the impact of incorporating them within RM image reconstruction, using carbon-11 phantom and clinical datasets on the HRRT. Results: The results obtained using these two isotopes illustrate that even small differences in positron range can result in different PSF maps, leading to further improvements in contrast recovery when used in image reconstruction. The difference is more pronounced in the centre of the field-of-view where the full width at half maximum (FWHM) from the positron range has a larger contribution to the overall FWHM compared to the edge where the parallax error dominates the overall FWHM. Conclusions: Based on the proposed methodology, measured isotope-specific and spatially variant PSFs can be reliably derived and used for improved spatial resolution and variance performance in resolution

  19. Plasma input function determination for PET using a commercial laboratory robot

    Energy Technology Data Exchange (ETDEWEB)

    Alexoff, David L.; Shea, Colleen; Fowler, Joanna S.; King, Payton; Gatley, S. John; Schlyer, David J.; Wolf, Alfred P

    1995-10-01

    A commercial laboratory robot system (Zymate PyTechnology II Laboratory Automation System) was interfaced to standard and custom laboratory equipment and programmed to perform rapid radiochemical assays necessary for plasma input function determination in quantitative PET studies in humans and baboons. A Zymark XP robot arm was used to carry out two assays: (1) the determination of total plasma radioactivity concentrations in a series of small-volume whole blood samples and (2) the determination of unchanged (parent) radiotracer in plasma using only solid phase extraction methods. Steady state robotic throughput for determination of total plasma radioactivity in whole blood samples (0.350 mL) is 14.3 samples/h, which includes automated centrifugation, pipetting, weighing and radioactivity counting. Robotic throughput for the assay of parent radiotracer in plasma is 4-6 samples/h depending on the radiotracer. Percents of total radioactivities present as parent radiotracers at 60 min. postinjection of 25 {+-} 5.0 (N 25), 26 {+-} 6.8 (N = 68), 13 {+-} 4.4 (N = 30), 32 {+-} 7.2 (N = 18), 16 {+-} 4.9 (N = 20), were obtained for carbon-11 labeled benztropine, raclopride, methylphenidate, SR 46349B (trans, 4-[(3Z)3-(2-dimethylamino-ethyl) oxyimino-3 (2-fluorophenyl)propen-1-yl]phenol), and cocaine respectively in baboon plasma and 84 {+-} 6.4 (N = 9), 18 {+-} 11 (N = 10), 74 {+-} 5.7 (N = 118) and 16 {+-} 3.7 (N = 18) for carbon-11 labeled benztropine, deprenyl, raclopride, and methylphenidate respectively in human plasma. The automated system has been used for more than 4 years for all plasma analyses for 7 different C-11 labeled compounds used routinely in our laboratory. The robotic radiotracer assay runs unattended and includes automated cleanup procedures that eliminates all human contact with plasma-contaminated containers.

  20. Plasma input function determination for PET using a commercial laboratory robot

    International Nuclear Information System (INIS)

    A commercial laboratory robot system (Zymate PyTechnology II Laboratory Automation System) was interfaced to standard and custom laboratory equipment and programmed to perform rapid radiochemical assays necessary for plasma input function determination in quantitative PET studies in humans and baboons. A Zymark XP robot arm was used to carry out two assays: (1) the determination of total plasma radioactivity concentrations in a series of small-volume whole blood samples and (2) the determination of unchanged (parent) radiotracer in plasma using only solid phase extraction methods. Steady state robotic throughput for determination of total plasma radioactivity in whole blood samples (0.350 mL) is 14.3 samples/h, which includes automated centrifugation, pipetting, weighing and radioactivity counting. Robotic throughput for the assay of parent radiotracer in plasma is 4-6 samples/h depending on the radiotracer. Percents of total radioactivities present as parent radiotracers at 60 min. postinjection of 25 ± 5.0 (N 25), 26 ± 6.8 (N = 68), 13 ± 4.4 (N = 30), 32 ± 7.2 (N = 18), 16 ± 4.9 (N = 20), were obtained for carbon-11 labeled benztropine, raclopride, methylphenidate, SR 46349B (trans, 4-[(3Z)3-(2-dimethylamino-ethyl) oxyimino-3 (2-fluorophenyl)propen-1-yl]phenol), and cocaine respectively in baboon plasma and 84 ± 6.4 (N = 9), 18 ± 11 (N = 10), 74 ± 5.7 (N = 118) and 16 ± 3.7 (N = 18) for carbon-11 labeled benztropine, deprenyl, raclopride, and methylphenidate respectively in human plasma. The automated system has been used for more than 4 years for all plasma analyses for 7 different C-11 labeled compounds used routinely in our laboratory. The robotic radiotracer assay runs unattended and includes automated cleanup procedures that eliminates all human contact with plasma-contaminated containers

  1. Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β)

    International Nuclear Information System (INIS)

    Introduction: The dysfunction of glycogen synthase kinase-3β (GSK-3β) has been implicated in a number of diseases, including Alzheimer’s disease. The ability to non-invasively quantify GSK-3β activity in vivo is therefore of critical importance, and this work is focused upon development of inhibitors of GSK-3β radiolabeled with carbon-11 to examine quantification of the enzyme using positron emission tomography (PET) imaging. Methods: 11C PyrATP-1 was prepared from the corresponding desmethyl-piperazine precursor in an automated synthesis module. In vivo rodent and primate imaging studies were conducted on a Concorde MicroPET P4 scanner to evaluate imaging properties and in vitro autoradiography studies with rat brain samples were carried out to examine specific binding. Results: 2035 ± 518 MBq (55 ± 14 mCi) of [11C]PyrATP-1 was obtained (1%–2% non-corrected radiochemical yield at end-of-synthesis based upon [11C]CO2) with high chemical (> 95%) and radiochemical (> 99%) purities, and good specific activities (143 ± 52 GBq/μmol (3874 ± 1424 Ci/mmol)), n = 5. In vivo microPET imaging studies revealed poor brain uptake in rodents and non-human primates. Pretreatment of rodents with cyclosporin A resulted in moderately increased brain uptake suggesting Pgp transporter involvement. Autoradiography demonstrated high levels of specific binding in areas of the rodent brain known to be rich in GSK-3β. Conclusion: 11C PyrATP-1 is readily synthesized using standard carbon-11 radiochemistry. However the poor brain uptake in rodents and non-human primates indicates that the radiotracer is not suitable for the purposes of quantifying GSK-3β in neurological and psychiatric disorders

  2. Immune function and hematology of male cotton rats (Sigmodon hispidus) in response to food supplementation and methionine

    Science.gov (United States)

    Webb, R.E.; Leslie, David M., Jr.; Lochmiller, R.L.; Masters, R.E.

    2003-01-01

    We examined effects of supplementation of food quantity and quality (=enhanced methionine) on hematologic and immunologic parameters of wild, but enclosed, adult male cotton rats (Sigmodon hispidus) in north-central Oklahoma. Sheet metal enclosures were stocked with a high density of wild-caught cotton rats (160 animals/ha) and randomly assigned a treatment of no supplementation, mixed-ration supplementation or methionine-enhanced supplementation. Aside from small increases in counts of red blood cells and hematocrit levels, most indices of erythrocytic characteristics were not affected by supplementation with the mixed-ration or enhanced methionine. In contrast, platelet counts were highest in mixed-ration and methionine treatments and counts of total white blood cells were highest with methionine supplementation, albeit relative proportions of different leukocytes did not differ among treatments. Immunologically, neither delayed-type hypersensitivity response nor hemolytic-complement activity differed among treatments. Supplementation of food quantity and quality did not broadly affect hematologic parameters and immune function of male cotton rats, but enhanced platelet and leukocyte counts may confer advantages to overall health. Clarification of the role of such effects on population limitation or regulation requires additional research. ?? 2003 Elsevier Inc. All rights reserved.

  3. Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes

    Directory of Open Access Journals (Sweden)

    Hurley Thomas D

    2007-12-01

    Full Text Available Abstract Background Methionine aminopeptidase is a potential target of future antibacterial and anticancer drugs. Structural analysis of complexes of the enzyme with its inhibitors provides valuable information for structure-based drug design efforts. Results Five new X-ray structures of such enzyme-inhibitor complexes were obtained. Analysis of these and other three similar structures reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65 (the YHGY loop that is an integral part of the substrate and inhibitor binding pocket. This adaptability is important for accommodating inhibitors with variations in size. When compared with the human isozymes, this loop either becomes buried in the human type I enzyme due to an N-terminal extension that covers its position or is replaced by a unique insert in the human type II enzyme. Conclusion The adaptability of the YHGY loop in E. coli methionine aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables the enzyme active pocket to accommodate inhibitors of differing size. The differences in this adaptable loop between the bacterial and human methionine aminopeptidases is a structural feature that can be exploited to design inhibitors of bacterial methionine aminopeptidases as therapeutic agents with minimal inhibition of the corresponding human enzymes.

  4. Genetic Polymorphism of Folate and Methionine Metabolizing Enzymes and their Susceptibility to Malignant Lymphoma

    International Nuclear Information System (INIS)

    Folate and methionine metabolism is involved in DNA synthesis and methylation. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylene-tetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms MTHFR 677 C-7T and MTHFR 1298 A-7C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5, 10 vm ethylene-tetrahydrofolate and results in a reduced incidence of DNA double strand breakage. The MS 2756 A-7G polymorphism also reduces the enzyme activity and results in the hypo methylation of DNA. Patients and Methods: To test this hypothesis, genetic polymorphisms in the folate metabolic pathway were investigated using the DNA from a case-control study on 31 patients having malignant lymphoma from the Oncology Outpatient Clinic of the New Children's Hospital, Cairo University and 30 controls who were actually normal children attending for vaccination to the same hospital. We found that there is a higher susceptibility with the MTHFR 677CC and MTHFR 1298 AA genotypes (OR=4.3, 95% CI 1.12-16). When those harbor at least one variant allele in either polymorphism of MTHFR they were defined as reference. For the MS 2756 AG genotype polymorphism there was also a higher susceptibility to developing malignant lymphoma (OR=2.6; 95% CI 1.16.4). Results suggest that folate and methionine metabolism may play an important role in the pathogenesis of malignant lymphoma. Further studies to confirm this association and detailed biologic mechanisms are now required

  5. Metabolic adaptation of Ralstonia solanacearum during plant infection: a methionine biosynthesis case study.

    Directory of Open Access Journals (Sweden)

    Laure Plener

    Full Text Available MetE and MetH are two distinct enzymes that catalyze a similar biochemical reaction during the last step of methionine biosynthesis, MetH being a cobalamin-dependent enzyme whereas MetE activity is cobalamin-independent. In this work, we show that the last step of methionine synthesis in the plant pathogen Ralstonia solanacearum is under the transcriptional control of the master pathogenicity regulator HrpG. This control is exerted essentially on metE expression through the intermediate regulator MetR. Expression of metE is strongly and specifically induced in the presence of plant cells in a hrpG- and metR-dependent manner. metE and metR mutants are not auxotrophic for methionine and not affected for growth inside the plant but produce significantly reduced disease symptoms on tomato whereas disruption of metH has no impact on pathogenicity. The finding that the pathogen preferentially induces metE expression rather than metH in the presence of plant cells is indicative of a probable metabolic adaptation to physiological host conditions since this induction of metE occurs in an environment in which cobalamin, the required co-factor for MetH, is absent. It also shows that MetE and MetH are not functionally redundant and are deployed during specific stages of the bacteria lifecycle, the expression of metE and metH being controlled by multiple and distinct signals.

  6. Basic study of entire whole-body PET scanners based on the OpenPET geometry

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Eiji, E-mail: rush@nirs.go.j [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yamaya, Taiga; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan)

    2010-09-21

    A conventional PET scanner has a 15-25 cm axial field-of-view (FOV) and images a whole body using about six bed positions. An OpenPET geometry can extend the axial FOV with a limited number of detectors. The entire whole-body PET scanner must be able to process a large amount of data effectively. In this work, we study feasibility of the fully 3D entire whole-body PET scanner using the GATE simulation. The OpenPET has 12 block detector rings with the ring diameter of 840 mm and each block detector ring consists of 48 depth-of-interaction (DOI) detectors. The OpenPET has the axial length of 895.95 mm with five parts of 58.95 mm open gaps. The OpenPET has higher single data loss than a conventional PET scanner at grouping circuits. NECR of the OpenPET decreases by single data loss. But single data loss is mitigated by separating the axially arranged detector into two parts. Also, multiple coincidences are found to be important for the entire whole-body PET scanner. The entire whole-body PET scanner with the OpenPET geometry promises to provide a large axial FOV with the open space and to have sufficient performance values. But single data loss at the grouping circuits and multiple coincidences are limited to the peak noise equivalent count rate (NECR) for the entire whole-body PET scanner.

  7. PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcelo A.; Schulthess, Gustav von; Veit-Haibach, Patrick [University Hospital Zurich, Department Medical Radiology, Nuclear Medicine, Zurich (Switzerland); University Hospital Zurich, Department Medical Radiology, Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Zurich (Switzerland); Kubik-Huch, Rahel A.; Freiwald-Chilla, Bianka [Kantonsspital Baden AG, Department of Radiology, Baden (Switzerland); Hauser, Nik [Kantonsspital Baden AG, Department of Gynaecology, Baden (Switzerland); Froehlich, Johannes M. [Guerbet AG, Zurich (Switzerland)

    2015-08-15

    To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. (orig.)

  8. Present and future aspects of PET examinations

    International Nuclear Information System (INIS)

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

  9. Functional diagnosis of cancer using PET

    International Nuclear Information System (INIS)

    Clinical application of PET imaging of auto activation derived from C-12 ion radiotherapy was studied. We have introduced the patient fixation system for auto activation PET measurements. Using this fixation system, we can get PET images with the same patient positioning as with patient positioning of Heavy Ion Medical Accelerator in Chiba (HIMAC) therapy planning CT. It is very important to perform the PET measurements under exactly same patient positioning as HIMAC therapy to compare RI distributions. We performed some clinical PET measurements and got superimposed images of PET and CT planning of HIMAC therapy patients. We tried to use a fitting method, automatic multi modality image registration method (AMIR method) of the Dr. View applications. In this method, we fitted the transmission images of PET to planning CT images at the start, and then superimposed emission images on the planning CT images. Our fitting results were relatively good. But some problems were found out. The most important one was the difference of patients breathing phases between PET examination and CT imaging. The difference of patients breathing phases should cause fitting errors of the fusion images of PET and CT especially in chest and abdominal regions. We think that the breathing phases of PET and CT should be in phase with each other to perform precise fitting of the two modalities. (author)

  10. Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor

    OpenAIRE

    Wang, Jieyi; Tucker, Lora A; Stavropoulos, Jason; Qian ZHANG; Wang, Yi-Chun; Bukofzer, Gail; Niquette, Amanda; Meulbroek, Jonathan A; Barnes, David M; Shen, Jianwei; Bouska, Jennifer; Donawho, Cherrie; Sheppard, George S.; Bell, Randy L.

    2008-01-01

    This laboratory and others have shown that agents that inhibit the in vitro catalytic activity of methionine aminopeptidase-2 (MetAP2) are effective in blocking angiogenesis and tumor growth in preclinical models. However, these prototype MetAP2 inhibitors are clearly not optimized for therapeutic use in the clinic. We have discovered an orally active class of MetAP2 inhibitors, the anthranilic acid sulfonamides exemplified by A-800141, which is highly specific for MetAP2. This orally bioavai...

  11. Investigation of the metal binding site in methionine aminopeptidase by density functional theory

    DEFF Research Database (Denmark)

    Jørgensen, Anne Techau; Norrby, Per-Ola; Liljefors, Tommy

    2002-01-01

    All methionine aminopeptidases exhibit the same conserved metal binding site. The structure of this site with either Co2+ ions or Zn2+ ions was investigated using density functional theory. The calculations showed that the structure of the site was not influenced by the identity of the metal ions...... bridging oxygen, which is part of either a water molecule or a hydroxide ion. Within the site of hMetAP-2 the results strongly indicate that a hydroxide ion bridges the metal ions. By contrast, the nature of the oxygen bridging the metal ions within the metal binding site of eMetAP-1 cannot be determined...

  12. Nutrient digestibility, carcass characteristics and plasma metabolites in kids fed diets supplemented with chromium methionine

    OpenAIRE

    Emami, A.; A. Zali; M. GANJKHANLOU; A. AKBARI AFJANI

    2012-01-01

    This study was carried out to evaluate the effects of different levels of chromium methionine (CrMet) on nutrient digestibility, carcass characteristics and plasma metabolites of male kids. Thirty-two male Mahabadi goat kids (average initial body weight (BW) = 22±2 kg, 4 months) were allocated in a completely randomized design with four treatments: 1) control (without Cr), 2) 0.5, 3) 1 and 4) 1.5 mg Cr as Cr-Met/animal/day. Diets were same (ratio of forage: concentrate was 30:70) except for t...

  13. Clinical Application of {sup 18}F-FDG PET and PET-CT in Adrenal Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyung Hoon; Choi, Duck Joo; Lee, Min Kyung; Choe, Won Sick [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2008-12-15

    Adrenal tumors are increasingly detected by widespread use of anatomical imaging such as CT, MRI, etc. For these adrenal tumors, differentiation between malignancy and benignancy is very important. In diagnostic assessment of adrenal tumor, {sup 18}F-FDG PET and PET-CT have been reported to have high diagnostic performance, especially, very excellent performance in evaluation of adrenal metastasis in the oncologic patient. In cases of adrenal incidentalomas, {sup 18}F-FDG PET or PET-CT is helpful if CT or chemical-shift MRI is inconclusive. {sup 18}F-FDG PET and PET-CT may be applied to the patients with MIBG-negative pheochromocytomas. In summary, {sup 18}F-FDG PET and PET-CT are expected to be effective diagnostic tools in the management of adrenal tumor.

  14. A Riboswitch Regulates Expression of the Coenzyme B12-Independent Methionine Synthase in Mycobacterium tuberculosis: Implications for Differential Methionine Synthase Function in Strains H37Rv and CDC1551▿ †

    OpenAIRE

    Warner, Digby F.; Savvi, Suzana; Mizrahi, Valerie; Dawes, Stephanie S.

    2007-01-01

    We observed vitamin B12-mediated growth inhibition of Mycobacterium tuberculosis strain CDC1551. The B12 sensitivity was mapped to a polymorphism in metH, encoding a coenzyme B12-dependent methionine synthase. Vitamin B12-resistant suppressor mutants of CDC1551 containing mutations in a B12 riboswitch upstream of the metE gene, which encodes a B12-independent methionine synthase, were isolated. Expression analysis confirmed that the B12 riboswitch is a transcriptional regulator of metE in M. ...

  15. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

    DEFF Research Database (Denmark)

    Boellaard, Ronald; O'Doherty, Mike J; Weber, Wolfgang A; Mottaghy, Felix M; Lonsdale, Markus N; Stroobants, Sigrid G; Oyen, Wim J G; Kotzerke, Joerg; Hoekstra, Otto S; Pruim, Jan; Marsden, Paul K; Tatsch, Klaus; Hoekstra, Corneline J; Visser, Eric P; Arends, Bertjan; Verzijlbergen, Fred J; Zijlstra, Josee M; Comans, Emile F I; Lammertsma, Adriaan A; Paans, Anne M; Willemsen, Antoon T; Beyer, Thomas; Bockisch, Andreas; Schaefer-Prokop, Cornelia; Delbeke, Dominique; Baum, Richard P; Chiti, Arturo; Krause, Bernd J

    2010-01-01

    The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography......-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information....

  16. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  17. Increase of fungitoxicity of mercuric chloride by methionine, ethionine and S-methylcysteine. [Aspergillus niger; Cladosporium cucumerinum; Scopulariopsis brevicaulis

    Energy Technology Data Exchange (ETDEWEB)

    Vonk, J.W.; Sijpesteijn, A.K.

    1974-01-01

    The fungitoxicity of mercuric chloride to Aspergillus niger was increased in the presence of D-, L-, DL-methionine, DL-ethionine, DL-S-methylcysteine or sodium methylmercaptide. The same effect was observed with methionine for two other fungi investigated: Cladosporium cucumerinum and Scopulariopsis brevicaulis. It is suggested that this effect can be ascribed to the formation of CH/sub 3/SHg/sup +/ or (CH/sub 3/S)/sub 2/Hg, or the corresponding ethyl compounds. CH/sub 3/SHgCl and (CH/sub 3/S)/sub 2/Hg were synthetically prepared and proved indeed far more fungitoxic than HgCl/sub 2/. The hypothesis was further substantiated by the observation that A. niger rapidly converts DL-methionine into CH/sub 3/SH, which undoubtedly reacts with Hg/sup 2 +/ to give the above mentioned methylthiomercury compounds. 16 references, 2 figures, 2 tables.

  18. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian;

    2013-01-01

    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  19. Joint PET-MR respiratory motion models for clinical PET motion correction.

    Science.gov (United States)

    Manber, Richard; Thielemans, Kris; Hutton, Brian F; Wan, Simon; McClelland, Jamie; Barnes, Anna; Arridge, Simon; Ourselin, Sébastien; Atkinson, David

    2016-09-01

    Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUV(peak) and SUV(max)) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required. PMID:27524409

  20. Child vs. Pet: The Effect of Abortion Legalization on the Demand for Pets

    OpenAIRE

    Youjin Hahn; Liang Choon Wang; Hee-Seung Yang

    2012-01-01

    This paper examines whether abortion legalization led to increased demand for pets in the United States. We compare women living in early-legalizing states, whose peak childbearing years occurred in the early 1970s, to women in other states and cohorts and estimate their likelihood of pet ownership and time spent on pets after their peak childbearing years were over. We find the probability of owning any pet is approximately 9.6 percentage points higher for women affected by abortion legaliza...

  1. The Role of F-18- FDG PET and PET/CT in Lung Cancer

    OpenAIRE

    Tümkaya, Evren; Büyükdereli, Gülgün

    2013-01-01

    Positron emission tomography (PET) has the unique ability to image bodily functions, such as blood flow, oxygen use, and glucose metabolism. PET imaging in combination with computerized tomography (CT) offers a high sensitivity scan for metabolic activity with precise anatomical localization. PET/CT with the glucose analog 18F-fluorodeoxyglucose (FDG) has become an essential tool for the work-up of patients with cancer for clinical practice. F-18-FDG PET/CT provides valuable information about...

  2. Validation of peneloPET simulations of the Biograph PET/CT scanner with TOF capabilities

    OpenAIRE

    Abushab, K. M.; Herraiz, J. L.; Vicente, E.; España, Samuel; Vaquero, Juan José; Udías, José Manuel

    2010-01-01

    Monte Carlo simulations are currently widely used in positron emission tomography (PET) imaging for optimizing detector design and acquisition protocols, and for developing and assessing corrections and reconstruction methods. PeneloPET is a Monte Carlo code for PET simulations with basic components of detector geometry, acquisition electronics and material and source definitions. The purpose of the present study was to validate the simulations of the Siemens Biograph PET/CT scanner with TOF ...

  3. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

    Science.gov (United States)

    Lees, Emma K; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W; Delibegovic, Mirela

    2014-10-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. PMID:24935677

  4. Structural effects of methionine oxidation on isolated subdomains of human fibrin D and αC regions.

    Science.gov (United States)

    Burney, Patrick R; White, Nathan; Pfaendtner, Jim

    2014-01-01

    Oxidation of key methionine residues on fibrin leads to altered fibrin polymerization producing severely altered fibrin gel structure and function. This is important because fibrinogen and its modification by oxidative stress have been implicated as key contributors to both pathological thrombotic and hemorrhagic diseases ranging from cardiovascular thrombosis to the acute coagulopathy of trauma. However, how oxidation leads to altered fibrin polymerization remains poorly understood at the molecular level. We have applied a powerful and novel well-tempered ensemble parallel tempering (PT-WTE) technique along with conventional molecular dynamics (MD) simulation to investigate the molecular-level consequences of selective methionine oxidation of fibrinogen. We offer new insights into molecular mechanisms of oxidation-induced changes in fibrin polymerization, while focusing on the D region knob 'B' and hole 'b' interaction and αC-domain interactions, both of which are hypothesized to contribute to the lateral aggregation mechanism of fibrin fibrils. Methionine oxidation did not alter the native state or the stability of a bound knob 'B' surrogate when interacting with hole 'b' in the D region. However, applying PT-WTE simulation to a human homology model of the bovine N-terminal subdomain fragment from the αC-domain revealed that methionine oxidation altered the conformation of the hairpin-linking region to favor open rather than closed hairpin structures. We attribute this alteration to the disruption of the hairpin-linking region's conformation, with oxidation increasing the radius of gyration for this segment. This result is in agreement with experimental data demonstrating decreased fibrin protofibril lateral aggregation when methionine oxidation is present in the same αC-domain fragment. Therefore, single methionine oxidation within the αC-domain is a likely molecular mechanism. PMID:24475207

  5. Structural effects of methionine oxidation on isolated subdomains of human fibrin D and αC regions.

    Directory of Open Access Journals (Sweden)

    Patrick R Burney

    Full Text Available Oxidation of key methionine residues on fibrin leads to altered fibrin polymerization producing severely altered fibrin gel structure and function. This is important because fibrinogen and its modification by oxidative stress have been implicated as key contributors to both pathological thrombotic and hemorrhagic diseases ranging from cardiovascular thrombosis to the acute coagulopathy of trauma. However, how oxidation leads to altered fibrin polymerization remains poorly understood at the molecular level. We have applied a powerful and novel well-tempered ensemble parallel tempering (PT-WTE technique along with conventional molecular dynamics (MD simulation to investigate the molecular-level consequences of selective methionine oxidation of fibrinogen. We offer new insights into molecular mechanisms of oxidation-induced changes in fibrin polymerization, while focusing on the D region knob 'B' and hole 'b' interaction and αC-domain interactions, both of which are hypothesized to contribute to the lateral aggregation mechanism of fibrin fibrils. Methionine oxidation did not alter the native state or the stability of a bound knob 'B' surrogate when interacting with hole 'b' in the D region. However, applying PT-WTE simulation to a human homology model of the bovine N-terminal subdomain fragment from the αC-domain revealed that methionine oxidation altered the conformation of the hairpin-linking region to favor open rather than closed hairpin structures. We attribute this alteration to the disruption of the hairpin-linking region's conformation, with oxidation increasing the radius of gyration for this segment. This result is in agreement with experimental data demonstrating decreased fibrin protofibril lateral aggregation when methionine oxidation is present in the same αC-domain fragment. Therefore, single methionine oxidation within the αC-domain is a likely molecular mechanism.

  6. Pet Ownership and Evacuation Prior to Hurricane Irene.

    Science.gov (United States)

    Hunt, Melissa G; Bogue, Kelsey; Rohrbaugh, Nick

    2012-01-01

    Pet ownership has historically been one of the biggest risk factors for evacuation failure prior to natural disasters. The forced abandonment of pets during Hurricane Katrina in 2005 made national headlines and led to the passage of the Pet Evacuation and Transportation Standards Act (PETS, 2006) which mandated local authorities to plan for companion animal evacuation. Hurricane Irene hit the East Coast of the United States in 2011, providing an excellent opportunity to examine the impact of the PETS legislation on frequency and ease of evacuation among pet owners and non-pet owners. Ninety pet owners and 27 non-pet owners who lived in mandatory evacuation zones completed questionnaires assessing their experiences during the hurricane and symptoms of depression, PTSD, dissociative experiences, and acute stress. Pet ownership was not found to be a statistical risk factor for evacuation failure. However, many pet owners who failed to evacuate continue to cite pet related reasons. PMID:26487162

  7. Pet Ownership and Evacuation Prior to Hurricane Irene

    Directory of Open Access Journals (Sweden)

    Nick Rohrbaugh

    2012-09-01

    Full Text Available Pet ownership has historically been one of the biggest risk factors for evacuation failure prior to natural disasters. The forced abandonment of pets during Hurricane Katrina in 2005 made national headlines and led to the passage of the Pet Evacuation and Transportation Standards Act (PETS, 2006 which mandated local authorities to plan for companion animal evacuation. Hurricane Irene hit the East Coast of the United States in 2011, providing an excellent opportunity to examine the impact of the PETS legislation on frequency and ease of evacuation among pet owners and non-pet owners. Ninety pet owners and 27 non-pet owners who lived in mandatory evacuation zones completed questionnaires assessing their experiences during the hurricane and symptoms of depression, PTSD, dissociative experiences, and acute stress. Pet ownership was not found to be a statistical risk factor for evacuation failure. However, many pet owners who failed to evacuate continue to cite pet related reasons.

  8. First PET scans in Estonia

    International Nuclear Information System (INIS)

    First PET scans in Estonia were performed on 25th November 2002 in North Estonia Regional Hospital, Tallinn. Six patients with melanoma underwent scanning with FDG. This event was a result of thorough extensive preparations first started in 2000 during the European Association of Nuclear Medicine congress in Paris. During the congress first contacts were made with providers of mobile PET units. At the same time negotiations were begun with potential FDG suppliers. For the introduction of PET in Estonia mobile truckmounted scanning technology was chosen due to low level of initial investments. Of particular importance was also availability of maintenance personnel from the device providers. A significant prerequisite was potential availability of FDG from the neighbourhood - Finland and Sweden. The latter avoided the necessity for investments into local cyclotrons and local FDG production. For the first scanning experience the dedicated truckmounted PET-camera Accel, Siemens was brought by the International Hospital Group (IHG, Amersfoort, Netherlands). The device arrived by ferry from Stockholm to Tallinn harbour at 10 o'clock in the morning and left by ferry for Helsinki at 23 o'clock. The team-on-truck consisted of one technician for device operation, two drivers and two company representatives. North Estonia Regional Hospital provided three additional technicians for patient preparation and FDG injection, one nuclear medicine doctor and one specialist of biomedical engineering and medical physics. The FDG was provided by MAP Medical Technologies, Schering, Helsinki, Finland. The shipments were made by air. This was possible due to small distance between Tallinn and Helsinki of approximately 80 km due to the regular flight connections between the two cities. The FDG was shipped in two lots with a time interval of 4 hours. The patient selection was based on clinical and histopathology data. In all six patients the exam was justified for detailied staging and

  9. Pet Store Loyalty in Malaysia

    OpenAIRE

    Leong, Yuen Yee

    2010-01-01

    Loyalty is open studied topic within the retailing and marketing discipline. A strong and profitable base of loyal customers is an asset to any organization, and is one of the epitomes of success for a company. The flourishing of large, specialty niche retailers like Starbucks, Victoria Secret and Barnes & Noble are stellar success stories that thrive on their troop of staunch followers. Pet retailing is a niche market which has its own interesting market characteristics. The emergence of ...

  10. Critical Care of Pet Birds.

    Science.gov (United States)

    Jenkins, Jeffrey Rowe

    2016-05-01

    Successful care of the critical pet bird patient is dependent on preparation and planning and begins with the veterinarian and hospital staff. An understanding of avian physiology and pathophysiology is key. Physical preparation of the hospital or clinic includes proper equipment and understanding of the procedures necessary to provide therapeutic and supportive care to the avian patient. An overview of patient intake and assessment, intensive care environment, and fluid therapy is included. PMID:27131161

  11. Introducing the PET Centre Bydgoszcz - Poland

    International Nuclear Information System (INIS)

    Opening the PET station held 26th February, 2003 was an excellent opportunity to present Regional Centre of Oncology in Bydgoszcz, the city in northern Poland. Department of Nuclear Medicine and its building, equipment, CT/PET station and scanning parameters, the cyclotron with basic technical data have been shortly described. A future of PET diagnostics in Poland taking into account the economical factors has been also discussed

  12. PET-CT imaging in pediatric oncology

    OpenAIRE

    McCarville, M. Beth

    2009-01-01

    Abstract Positron emission tomography (PET)-computed tomography (CT) is emerging as a valuable tool for assessing a wide variety of pediatric malignancies, including lymphomas, soft-tissue tumors, and bone sarcomas. PET-CT may provide information that is not apparent on conventional imaging performed to stage these diseases and monitor their response to treatment. The use of PET-CT in children requires an awareness of the technical and logistical issues unique to this patient population. In a...

  13. FDG-PET imaging in hematological malignancies.

    Science.gov (United States)

    Valls, L; Badve, C; Avril, S; Herrmann, K; Faulhaber, P; O'Donnell, J; Avril, N

    2016-07-01

    The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques. PMID:27090170

  14. PET/MR: a paradigm shift

    OpenAIRE

    Gaertner, Florian C.; Furst, Sebastian; Schwaiger, Markus

    2013-01-01

    Abstract More than a decade ago, multimodality imaging was introduced into clinical routine with the development of the positron emission tomography (PET)/computed tomography (CT) technique. Since then, PET/CT has been widely accepted in clinical imaging and has emerged as one of the main cancer imaging modalities. With the recent development of combined PET/magnetic resonance (MR) systems for clinical use, a promising new hybrid imaging modality is now becoming increasingly available. The co...

  15. Methionine synthase A2756G variation is associated with the risk of retinoblastoma in Iranian children.

    Science.gov (United States)

    Akbari, Mohammad Taghi; Naderi, Asieh; Saremi, Leila; Sayad, Arezou; Irani, Shiva; Ahani, Ali

    2015-12-01

    Association of epigenetic modifications with cancer has been widely studied. Gene-specific hypermethylation and global DNA hypomethylation are the most frequently observed patterns in great number of tumors. The methionine synthase (MTR) gene plays key role in maintaining adequate intracellular folate, methionine and normal homocysteine concentrations and, its polymorphism have been associated with the risk of retinoblastoma and other neoplasms. We evaluated the association of MTR A2756G polymorphism with the risk of retinoblastoma in an Iranian population. Totally, 150 retinoblastoma patients and 300 individuals with no family history of cancer as control were included in this study. Genotyping of the A2756G polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) using the restriction enzymes HaeIII. Our results showed that the "G" was the minor allele with a frequency of 31.7% and 20.3% in both retinoblastoma and control groups, respectively. The frequency of the 2756GG genotype (P=0.023) and 2756G allele (P=0.0001) were significantly higher in the patients than control group, respectively. Individual with the 2756GG genotype had a 2.99 fold increased risk for retinoblastoma. According to our results, the MTR A2756G polymorphism was associated with the risk of retinoblastoma in Iranian patients. PMID:26595280

  16. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.

    Science.gov (United States)

    Hine, Christopher; Mitchell, James R

    2015-08-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action. PMID:25523462

  17. Expression, purification and crystallization of l-methionine γ-lyase 2 from Entamoeba histolytica

    International Nuclear Information System (INIS)

    l-Methionine γ-lyase 2 from E. histolytica, a key enzyme in sulfur-containing amino-acid degradation in this protozoan parasite, has been crystallized in a form suitable for X-ray structure analysis. l-Methionine γ-lyase (MGL) is considered to be an attractive target for rational drug development because the enzyme is absent in mammalian hosts. To enable structure-based design of drugs targeting MGL, one of the two MGL isoenzymes (EhMGL2) was crystallized in the orthorhombic space group P212121, with unit-cell parameters a = 88.89, b = 102.68, c = 169.87 Å. The crystal diffracted to a resolution of 2.0 Å. The presence of a tetramer in the asymmetric unit (4 × 43.1 kDa) gives a Matthews coefficient of 2.2 Å3 Da−1. The structure was solved by the molecular-replacement method and structure refinement is now in progress

  18. Progress in the microbial production of S-adenosyl-L-methionine.

    Science.gov (United States)

    Chen, Hailong; Wang, Zhilai; Cai, Haibo; Zhou, Changlin

    2016-09-01

    S-Adenosyl-L-methionine (SAM), which exists in all living organisms, serves as an activated group donor in a range of metabolic reactions, including trans-methylation, trans-sulfuration and trans-propylamine. Compared with its chemical synthesis and enzyme catalysis production, the microbial production of SAM is feasible for industrial applications. The current clinical demand for SAM is constantly increasing. Therefore, vast interest exists in engineering the SAM metabolism in cells for increasing product titers. Here, we provided an overview of updates on SAM microbial productivity improvements with an emphasis on various strategies that have been used to enhance SAM production based on increasing the precursor and co-factor availabilities in microbes. These strategies included the sections of SAM-producing microbes and their mutant screening, optimization of the fermentation process, and the metabolic engineering. The SAM-producing strains that were used extensively were Saccharomyces cerevisiae, Pichia pastoris, Candida utilis, Scheffersomyces stipitis, Kluyveromyces lactis, Kluyveromyces marxianus, Corynebacterium glutamicum, and Escherichia coli, in addition to others. The optimization of the fermentation process mainly focused on the enhancement of the methionine, ATP, and other co-factor levels through pulsed feeding as well as the optimization of nitrogen and carbon sources. Various metabolic engineering strategies using precise control of gene expression in engineered strains were also highlighted in the present review. In addition, some prospects on SAM microbial production were discussed. PMID:27465853

  19. Expression, purification and crystallization of l-methionine γ-lyase 2 from Entamoeba histolytica

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Dan [Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamagata, Wataru; Kamei, Kaeko [Graduate School of Science and Technology, Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Nozaki, Tomoyoshi [Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Harada, Shigeharu, E-mail: harada@kit.ac.jp [Graduate School of Science and Technology, Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)

    2006-10-01

    l-Methionine γ-lyase 2 from E. histolytica, a key enzyme in sulfur-containing amino-acid degradation in this protozoan parasite, has been crystallized in a form suitable for X-ray structure analysis. l-Methionine γ-lyase (MGL) is considered to be an attractive target for rational drug development because the enzyme is absent in mammalian hosts. To enable structure-based design of drugs targeting MGL, one of the two MGL isoenzymes (EhMGL2) was crystallized in the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 88.89, b = 102.68, c = 169.87 Å. The crystal diffracted to a resolution of 2.0 Å. The presence of a tetramer in the asymmetric unit (4 × 43.1 kDa) gives a Matthews coefficient of 2.2 Å{sup 3} Da{sup −1}. The structure was solved by the molecular-replacement method and structure refinement is now in progress.

  20. Metal active site elasticity linked to activation of homocysteine in methionine synthases

    Energy Technology Data Exchange (ETDEWEB)

    Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.; Matthews, Rowena G.; Smith, Janet L.; Ludwig, Martha L. (Michigan)

    2008-04-02

    Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry upon binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.