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Synthesis of [11C]nicotinamide analogs for imaging of nicotinamide N‑methyltransferase activity
https://repo.qst.go.jp/records/76125
https://repo.qst.go.jp/records/761258b5cb3b6-053c-46e1-8149-615d2c4de7df
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-05-30 | |||||
| タイトル | ||||||
| タイトル | Synthesis of [11C]nicotinamide analogs for imaging of nicotinamide N‑methyltransferase activity | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Okamura, Toshimitsu
× Okamura, Toshimitsu× Ishii, Hideki× Kikuchi, Tatsuya× Okada, Maki× Wakizaka, Hidekatsu× Ming-Rong, Zhang× Okamura, Toshimitsu× Ishii, Hideki× Kikuchi, Tatsuya× Okada, Maki× Wakizaka, Hidekatsu× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide and various closely related structural analogs to form positively charged pyridinium ions and contributes to the nicotinamide clearance and xenobiotic detoxification. NNMT is expressed primarily in the liver but has been found in other tissues at lower levels. Recent studies have shown relationships between changes in NNMT expression and several diseases. In the brain, Parkinson's disease patients have higher levels of NNMT protein and activity compared with normal subjects. In vivo imaging of NNMT activity would therefore be helpful for elucidation of pathological conditions. Here, we present the synthesis of [11C]nicotinamide analogs for imaging NNMT activity in the brain. To find a blood-brain barrier permeable tracer with the moderate methylation rate, which is required for NNMT imaging, five candidate tracers were designed in consideration of kinetic parameters of NNMT substrates [1]. Methods [11C]Nicotinamide, 4-methyl[11C]nicotinamide, and 3-quinoline[11C]carboxamide were synthesized by the Pd(0)-mediated [11C]carbomethoxylation of the corresponding pinacol esters with [11C]carbon monoxide in methanol followed by hydrolysis with aqueous ammonia solution. [11C]Thionicotinamide and 4-methylpyridine-3-[11C]carbothioamide were synthesized by the thoiamidation of the corresponding [11C]cyanopyridines using sodium hydrogen sulfide in N,N-dimethylformamide (DMF) at 90°C. The [11C]cyanopyridines were prepared by the reaction of the bromo precursors with [11C]ammonium cyanide in DMF at 180°C. Results The radiochemical yields of the isolated [11C]nicotinamide, 4-methyl[11C]nicotinamide, 3-quinoline[11C]carboxamide, [11C]thionicotinamide, and 4-methylpyridine-3-[11C]carbothioamide from [11C]carbon dioxide were 2.7 1.1%, 4.3 3.5%, 5.4 0.1%, 7.8 6.6%, and 4.0 3.5% (decay corrected to the end of bombardment), respectively. Their radiochemical purities were >95%, and molar activity was in the range of 7.4 to 82 GBq/μmol at the end of synthesis. Conclusions We have achieved the synthesis of the candidate tracers, [11C]nicotinamide analogs, for imaging NNMT activity in the brain. Further in vivo studies are in progress. References [1] van Haren MJ et al., Biochemistry, 2016, 55, 5307−5315 |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ISRS2019 (the 23rd International Symposium on Radiopharmaceutical Sciences) | |||||
| 発表年月日 | ||||||
| 日付 | 2019-05-28 | |||||
| 日付タイプ | Issued | |||||
