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，包括阿尔茨海默氏病在内的各种疾病患者的大脑中，尼古丁受体密度的变化发生了变化。这些休假激发了人们对脑烟碱受体在体内与核药物成像技术无创的分布的兴趣。因此，（S）5-碘互替氨酸（INC），在吡啶环的5位处于5位的（S） - 尼古丁类似碘，并被合成并评估为通过SPECT [125i] - （s） - INC与高特异性放射性合成的Spect [125i] - （s） - INC的潜在放射性药物。 INC对脑尼古丁受体的结合数据表明，INC的亲和力与（S） - 尼古丁的亲和力相同，比（R） - 源性异构体高80倍。小鼠的生物分布研究揭示了Inc的大脑吸收迅速而深刻。自显影术在大鼠中的区域脑分布研究揭示了[125 -i] -inc的积累与从体外研究中报道的尼古丁受体的分布非常相关。（R） - 源性异构体比（s） - 替代物显示出更快的大脑和局部脑分布。因此，INC在体内与脑尼古丁受体结合，因此123-I-INC可能是通过Spect用于体内脑烟碱受体研究的潜在放射性物体。