Development of the Colin transporter imaging agent for early diagnosis of Alzheimer's disease

开发用于阿尔茨海默病早期诊断的 Colin 转运蛋白显像剂

• 批准号: 23591813
• 负责人: SHIBA Kazuhiro
• 金额: $ 3.24万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591813/
• 关键词: アルツハイマー病; コリン作動性神経; 分子イメージング; アセチルコリントランスポーター; SPECT; コリン作動性神経系; ＳＰＥＣＴ; ＰＥＴ

We aimed at the development of the imaging probe for early diagnosis of Alzheimer's disease (AD). The cognitive impairment of AD is related to the cholinergic nerve system. we targeted the cholin transporter(ChT) and the acetylcholine transporter(VAChT) which exist in pre-synapse in cholinergic nerve. We synthesized the imaging probes with high affinity for ChT or VAChT. We could not develope a probe with high affinity for ChT in in vitro assays. However, I could synthesize a probe with high affinity for VAChT such as (-)-o-iododecalinvesamicol(OIDV). Radioiodinated OIDV ((-)-[I-125]OIDV) accumulated in rat brain through B.B.B. In vivo blocking and ex vivo autoradiography study showed that (-)-[I-125]OIDV selevtively accumulated in the VAChT in rat brain. These results showed that (-)-[I-125]OIDV bound selectively to VAChT in rat brain in vivo. Radioiodinated (-)-OIDV labeled with I-123 was suggested to be useful as a VAChT imaging agent for SPECT.

本课题旨在研制用于阿尔茨海默病（Alzheimer 'sdisease，AD）早期诊断的成像探针。AD的认知功能损害与胆碱能神经系统有关。本研究以胆碱能神经突触前膜的胆碱转运体（ChT）和乙酰胆碱转运体（VAChT）为靶点。我们合成了对ChT或VAChT具有高亲和力的成像探针。我们不能开发一个探针与ChT在体外试验中具有高亲和力。然而，我可以合成对VAChT具有高亲和力的探针，例如（-）-o-iodododecalinvesamicol（OIDV）。放射性碘标记的OIDV（（-）-[I-125]OIDV）通过B.B.B.体内阻断和离体放射自显影研究表明，（-）-[I-125]OIDV选择性蓄积于大鼠脑内VAChT。这些结果表明，（-）-[I-125]OIDV在体内选择性地与大鼠脑内VAChT结合。用I-123标记的放射性碘标记的（-）-OIDV被认为是有用的用于SPECT的VAChT显像剂。