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SYNTHESIS AND EVALUATION OF F-18-FEtP4A: A PET TRACER FOR IMAGING BRAIN ACETYLCHOLOLINESTERASE IN VIVO
https://repo.qst.go.jp/records/68561
https://repo.qst.go.jp/records/6856174265efe-a13b-4bef-918c-54cf0640e90e
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-07-03 | |||||
| タイトル | ||||||
| タイトル | SYNTHESIS AND EVALUATION OF F-18-FEtP4A: A PET TRACER FOR IMAGING BRAIN ACETYLCHOLOLINESTERASE IN VIVO | |||||
| 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 |
Zhang, Ming-Rong
× Zhang, Ming-Rong× Tsuchiyama, Akio× Kikuchi, Tatsuya× Furutsuka, Kenji× Yoshida, Yuichirou× Kida, Takayo× Noguchi, Junko× Haradahira, Terushi× Irie, Toshiaki× Suzuki, Kazutoshi× 張 明栄× 菊池 達矢× 古塚 賢士× 吉田 勇一郎× 原田平 輝志× 入江 俊章× 鈴木 和年 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | AIMS:Postmortem studies in patients with Alzheimer's disease showed a reduction in the activity of acetylcholinesterase (AchE) in the neocortex and hippocampus, compared with normal subjects. To measure brain AchE activity and further to elucidate the relationship between AchE and Alzheimer's disease, N-F-18-fluoroethyl-4-piperidyl acetate (F-18-FEtP4A), a F-18 analog of C-11-MP4A,was designed, synthesized and evaluated as a PET tracer for imaging AchE in vivo. Since this tracer possessing aminoalkyl acetate moiety is an acetylcholine derivative, F-18-FEtP4A may readily enter the brain and be specifically metabolized by AchE into the hydroxy product (F-18-FEtP4OH) which could be retained at the site of the hydrolysis enzyme in the brain. Moreover, the longer half-life of F-18 would provide the advantage to get more precise AchE activity information in the PET measurement, and to deliver the tracer to other facilities. Based on these considerations, F-18-FEtP4A may be expected to become a useful PET tracer for measurement of AchE activity in vivo. RESULTS: F-18-FEtP4A was prepared by reacting 4-piperidyl acetate (P4A) with F-18-fluoroethyl bromide (F-18-FEtBr), F-18-FEtBr/NaI or F-18-FEtOTf, respectively. The F-18-fluoroethylation efficiency was F-18-FEtOTf > F-18-FEtBr/NaI > F-18-FEtBr. The radiochemical purity and specific activity of F-18-FEtP4A was 97.3+/-1.9% and 270+/-45 GBq/mumol at EOS. In the final product solution (10 mL), the contamination of P4A was quantified using LC/MS and determined to be from 0.06 to 0.2 ppm. F-18-FEtP4A showed a rapid and high uptake into the mouse brain. Its initial uptake in the striatum, cerebral cortex and cerebellum was about 8% dose/g. After a high initial uptake, the radioactivity washout of F-18-FEtP4A from these regions followed monoexponential curves with similar elimination rates, with half-lives of about 30 min. The rank of radioactivity uptake of F-18-FEtP4A in these regions on the stationary phase (from 10 to 120 min after intravenous injection) agreed with that of AchE in the brain: striatum > cerebral cortex > cerebellum. The ex vivo autoradiogram on rat brain and PET on monkey brain showed a significant uptake of radioactivity in the striatum, the region with the highest AchE activity in brain. The chemical analysis of in vivo radioactive metabolites indicated that F-18-FEtP4A was hydrolyzed to F-18-FEtP4OH in the brain and blood, suggesting that the hydrolysis process was mediated by AchE. CONCLUSIONS: The in vivo evaluation of F-18-FEtP4A with mouse, rat and monkey showed that its regional distribution responded to the AchE activity pattern in the brain. Therefore, this tracer may be useful as an imaging agent for mapping the AchE activity in vivo and assessing the extent of cholinergic neuronal damage in Alzheimer's disease. |
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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 | Ninth International Works on Targetry and Target | |||||
| 発表年月日 | ||||||
| 日付 | 2002-05-30 | |||||
| 日付タイプ | Issued | |||||
