The development of the presynaptic cholinergic nerve molecules imaging agent for early diagnosis of Alzheimer's disease

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293273
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: Shiba Kazuhiro 金沢大学, 学際科学実験センター, 教授 (40143929)
• Co-Investigator(Kenkyū-buntansha): 北村 陽二 金沢大学, 学際科学実験センター, 准教授 (10368483) ; 小阪 孝史 金沢大学, 学際科学実験センター, 助教 (50579836)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: アセチルコリントランスポーター / アルツハイマー病 / 早期診断薬 / 分子イメージング

Outline of Final Research Achievements

The purpose of our study is to develop a novel PET imaging agent for early diagnosis of Alzheimer's disease, a severity diagnosis and an effect of treatment judgment. We targeted the acetylcholine transporter(VAChT) which exist in pre-synapse in cholinergic nerve system, which is related to the cognitive impairment of Alzheimer's disease. We newly synthesized (-)-o-[11C]methyl-trans-decalinvesamicol((-)-[11C]OMDV) and o-[77Br]Bromo-trans-decalinvesamicol([77Br]OBDV). (-)-[11C]OMDV and [77Br]OBDV showed a high binding affinity and selectivity for VAChT. In vivo studies demonstrated [11C]OMDV and [77Br]OBDV passage through the blood-brain barrier (BBB) and accumulation in the rat brain. The regional brain distribution of them was accordance with the density distribution of VAChT in brain. These results showed (-)-[11C]OMDV and [77Br]OBDV bound selectively to VAChT in vivo. (-)-[11C]OMDV and [77Br]OBDV was suggested to be useful as a VAChT imaging agent for PET.

Free Research Field

放射性医薬品化学