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In vivo imaging of nicotinic acetylcholine recptors in patients with Parkinson's disease

帕金森病患者烟碱乙酰胆碱受体的体内成像

基本信息

批准号：
16591202
负责人：
HASHIKAWA Kazuo
金额：
$ 2.24万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591202/
关键词：
Nicotinic receptor Parkinson's disease smokin SPECT

项目摘要

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain. Recently, 5-iodo-3-(2S)-azetidinylmethoxy) pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. The purpose of this study was to establish the quantitative measurements of nAChR binding by using 5IA SPECT and apply it to Parkinson's disorders.In the healthy volunteers, a 6-h dynamic SPECT acquisition was performed just after an I-123 5IA injection. Arterial blood samplings were done and pure 5IA concentrations were obtained by the TLC as input function. Two-compartment model (2C) and Logan plot were applied for kinetic analysis. Two scans were done in the smoking healthy volunteers, one was under smoking state and another was after 20-days smoke-free period. In the second, we performed 5IA SPECT studies in the patients with Parkinson's disease (PD).Good relationship was found between two distribution volumes (DVs) obtained by using 2C and Logan plot. DVs were th … More e highest in the thalamus, moderate in the pons, cerebellum, basal ganglia, lower in cerebral cortices. Good agreement was observed between DV values and results of autoradiographic experiments done in vitro for nAChR density in human brain. The DV during smoking were significantly lower than those under smoke-free state. The PD group showed a tendency for DV reduction in all brain regions and a statistically significant decrease in the brainstem and frontal cortex as compared with the control group. Although age, duration of disease, daily dose of levodopa, duration of PD medication use, and scores on the motor section of Unified Parkinson's Disease Rating Scale were not significantly correlated with DVs in any brain regions, high daily doses of dopamine agonist showed a significant negative correlation with DVs in the stratum, cerebellum, and temporal and parietal cortices.These findings suggest that patients with PD without dementia can show reductions in brain nAChRs, especially in the brainstem and frontal cortex. They also suggest that dopamine agonists can have a negative influence on the distribution of nAChRs. Our results also indicated that 5IA SPECT may become a useful method for the quantitative measurements for nAChRs in other neurodegenerative disorders. Less

神经元烟碱乙酰胆碱受体（nAChR）广泛分布于人脑中。最近，5-碘-3-（2S）-氮杂环丁烷甲氧基）吡啶（5IA）已被合成作为放射性配体与SPECT成像nAChR。为建立5IA SPECT定量测定nAChR结合的方法，并应用于帕金森病的研究，对健康志愿者注射I-123 5IA后立即进行6 h动态SPECT显像。进行动脉血取样，并通过TLC作为输入函数获得纯5IA浓度。采用二室模型（2C）和Logan图进行动力学分析。对吸烟的健康志愿者进行了两次扫描，一次是在吸烟状态下，另一次是在20天无烟期后。第二部分对帕金森病（PD）患者进行了5IA SPECT显像，用2C法和Logan法计算的分布容积（DV）之间有良好的相关性。DV是 ...更多信息丘脑最高，脑桥、小脑、基底节中等，大脑皮质较低。在人脑中nAChR密度的DV值和体外放射自显影实验的结果之间观察到良好的一致性。吸烟状态下的DV显著低于无烟状态下的DV。与对照组相比，PD组显示所有脑区DV减少的趋势，脑干和额叶皮质的DV减少具有统计学意义。尽管年龄、疾病持续时间、左旋多巴的日剂量、PD药物使用的持续时间和统一帕金森病评定量表的运动部分的分数与任何脑区域中的DV没有显著相关性，但高日剂量的多巴胺激动剂显示出与小脑、小脑、小脑和小脑中的DV显著负相关性。这些发现表明，没有痴呆的PD患者可以显示大脑nAChR的减少，特别是在脑干和额叶皮层。他们还表明，多巴胺激动剂可能对nAChR的分布产生负面影响。我们的研究结果还表明，5IA SPECT可能成为一个有用的方法，定量测量nAChRs在其他神经退行性疾病。少