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

我们的目标是开发用于阿尔茨海默病(AD)早期诊断的成像探针。阿尔茨海默病的认知损害与胆碱能神经系统有关。我们针对存在于胆碱能神经突触前的胆碱转运体和乙酰胆碱转运体。我们合成了对CHT或Vacht具有高亲和力的成像探针。我们无法在体外实验中开发出对CHT具有高亲和力的探针。然而，我可以合成一种对Vacht具有高亲和力的探针，如(-)-o-碘十二烷基氨基酚(OIDV)。放射性碘标记的OIDV((-)-[I-125]OIDV)通过B途径在大鼠脑内蓄积。体内阻断和体外放射自显影研究表明，(-)-[I-125]OIDV选择性地蓄积在大鼠脑内的Vacht。这些结果表明，(-)-[I-125]OIDV在体内选择性地与大鼠脑内的Vacht结合。I-123标记的放射性碘(-)-OIDV可作为SPECT的Vacht显像剂。

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.