Development of optically active radioligand for in vivo investigation of brain nicotine receptors.

开发用于脑尼古丁受体体内研究的光学活性放射性配体。

基本信息

批准号：
06672142
负责人：
SAJI Hideo
金额：
$ 1.34万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Changes in the density of nicotine receptors have recently been reported in the brains of patients with various disorders, including Alzheimer's disease. These obsevations have stimulated interest in means of imaging the distribution of brain nicotinic receptors noninvasively in vivo with nuclear medicinal imaging techniques such as SPECT.In this study, the superior radiation properties of 123-I for SPECT prompted us to synthesize a radioiodinated nicotine analog with high receptor affinity. Thus, (S) 5-iodonicotine (INC), an (S) -nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by SPECT.[125I] - (S) -INC was synthesized with high specific radioactivity. The binding data of INC for brain nicotine receptors revealed that the affinity of INC was the same as that of (S) -nicotine and 80-fold higher than the (R) -enantiomer. Biodistribution studies in mice disclosed that the brain uptake of INC was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125-I] -INC was correlated well with the distribution of nicotine receptors reported from in vitro studies. (R) -enantiomer showed more rapid washout the brain and smaller regional cerebral distribution than (S) -enantiomer. Thus, INC bound to brain nicotine receptors in vivo and therefore 123-I-INC may be a potential radioligand for use in in vivo cerebral nicotinic receptor studies by SPECT.

最近有报道称，患有各种疾病（包括阿尔茨海默病）的患者大脑中尼古丁受体密度发生了变化。这些观察结果激发了人们对使用 SPECT 等核医学成像技术对脑烟碱受体分布进行无创体内成像的兴趣。在这项研究中，123-I 用于 SPECT 的优异辐射特性促使我们合成放射性碘化尼古丁类似物高受体亲和力。因此，合成了 (S) 5-碘尼古丁 (INC)，一种在吡啶环 5 位上碘化的 (S)-尼古丁类似物，并评估其作为通过 SPECT 研究脑尼古丁受体的潜在放射性药物。 [125I] -合成的(S)-INC具有高比放射性。 INC与脑尼古丁受体的结合数据表明，INC的亲和力与(S)-尼古丁相同，比(R)-对映体高80倍。小鼠体内的生物分布研究表明，大脑对 INC 的吸收是快速而深刻的。通过放射自显影对大鼠进行的区域脑分布研究表明，[125-I]-INC 的积累与体外研究报告的尼古丁受体的分布密切相关。 (R)-对映异构体比(S)-对映异构体显示出更快速的大脑冲洗和更小的脑区域分布。因此，INC 在体内与脑烟碱受体结合，因此 123-I-INC 可能是用于 SPECT 体内脑烟碱受体研究的潜在放射性配体。