در هنگام جستجو کلمه در قسمت عنوان میتوانید کلمات مورد جستجو را با کاراکتر (-) جدا کنید.
کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asia Oceania Journal of Nuclear Medicine and Biology
- نوع مقاله: Journal Article
- کلمات کلیدی: PET,Radiosynthesis,11C-phenytoin,Radiopharmacy
- چکیده:
- چکیده انگلیسی: Objective(s): Phenytoin is an antiepileptic drug that is used worldwide. The whole-body pharmacokinetics of this drug have been extensively studied using 11C-phenytoin in small animals. However, because of the limited production amounts that are presently available, clinical 11C-phenytoin PET studies to examine the pharmacokinetics of phenytoin in humans have not yet been performed. We aimed to establish a new synthesis method to produce large amounts of 11C-phenytoin to conduct human studies.
Methods: 11C-methane was produced using an in-house cyclotron by the 14N (p, α) 11C nuclear reaction of 5 % of hydrogen containing 95 % of nitrogen gas. About 30 GBq of 11C-methane was then transferred to a
homogenization cell containing Fe2O3 powder mixed with Fe granules heated at 320 0C to yield 11C-phosgene. Xylene, 1,4-dioxane, and diethylene glycol diethyl ether (DEGDEE) were investigated as possible reaction solvents.
Results: The ratio of 11C-phenytoin radioactivity to the total 11C radioactivity in the reaction vessel (reaction efficiency) was 7.5% for xylene, 11% for 1,4-dioxane, and 37% for DEGDEE. The synthesis time was within 45 min from the end of bombardment until obtaining the final product. The radioactivity produced was more than 4.1 GBq in 10 mL of saline at the end of synthesis. The specific activity of the product ranged from 1.7 to 2.2
GBq/μmol. The quality of the 11C-phenytoin injection passed all criteria required for clinical use.
Conclusion: The use of DEGDEE as a solvent enabled the production of a large amount of 11C-phenytoin sufficient to enable PET studies examining the human pharmacokinetics of phenytoin.- انتشار مقاله: 16-12-1396
- نویسندگان: Yasukazu Kanai,Yoshinori Miyake,Jun Hatazawa
- مشاهده
- جایگاه : پژوهشی
- مجله: Asia Oceania Journal of Nuclear Medicine and Biology
- نوع مقاله: Journal Article
- کلمات کلیدی: 11C-DNP PET,oral dosing,Donepezil
- چکیده:
- چکیده انگلیسی: Objective(s): It is difficult to investigate the whole-body distribution of an orally administered drug by means of positron emission tomography (PET), owing to the short physical half-life of radionuclides, especially when 11C-labeled compounds are tested. Therefore, we aimed to examine the whole-body distribution of donepezil (DNP) as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP.
Methods: We studied 14 healthy volunteers, divided into group A (n=4) and group B (n=10). At first, we studied four females (mean age: 57.3±4.5 y), three of whom underwent 11C-DNP PET scan at 2.5 h after the oral administration of 1 mg and 30 μg of DNP, respectively, while one patient was scanned following the oral administration of 30 μg of DNP (group A). Then, we studied five females and five males (48.3±6.1 y), who underwent 11C-DNP PET scan, without the oral administration of DNP (group B). Plasma DNP concentration upon scanning was measured by tandem mass spectrometry. Arterialized venous blood samples were collected periodically to measure plasma radioactivity and metabolites. In group A, 11C-DNP PET scan of the brain and whole body continued for 60 and 20 min, respectively. Subjects in group B underwent sequential whole-body scan for 60 min. The regional uptake of 11C-DNP was analyzed by measuring the standard uptake value (SUV) through setting regions of interest on major organs with reference CT.
Results: In group A, plasma DNP concentration was significantly correlated with the orally administered dose of DNP. The mean plasma concentration was 2.00 nM (n=3) after 1 mg oral administration and 0.06 nM (n=4) after 30 μg oral administration. No significant difference in plasma radioactivity or fraction of metabolites was found between groups A and B. High 11C-DNP accumulation was found in the liver, stomach, pancreas, brain, salivary glands, bone marrow, and myocardium in groups A and B, in this order. No significant difference in SUV value was found among 11C-DNP PET studies after the oral administration of 1 mg of DNP, 30 μg of DNP, or no DNP.
Conclusion: The present study demonstrated that the whole-body distribution of DNP after the oral administration of pharmacological doses could be evaluated by 11C-DNP PET studies, combined with the oral administration of DNP.- انتشار مقاله: 10-01-1395
- نویسندگان: Ikuko Mochida,Eku Shimosegawa,Yasukazu Kanai,Sadahiro Naka,Jun Hatazawa,Keiko Matsunaga,Kayako Isohashi,Genki Horitsugi,Tadashi Watabe,Hiroki Kato
- مشاهده