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

神经元烟碱乙酰胆碱受体（nAChRs）广泛分布于人脑中。最近合成了5-碘-3-(2S)-氮杂基甲氧基)吡啶（5IA）作为SPECT成像nachr的放射配体。本研究的目的是利用5IA SPECT建立nAChR结合的定量测量方法，并将其应用于帕金森病。在健康志愿者中，在注射I-123 5IA后进行6小时动态SPECT采集。取动脉血标本，以TLC作为输入函数获得纯5IA浓度。动力学分析采用双室模型（2C）和Logan图。在吸烟健康的志愿者中进行了两次扫描，一次是在吸烟状态下，另一次是在20天无烟期后。在第二项研究中，我们对帕金森病（PD）患者进行了5IA SPECT研究。利用2C法得到的两个分布体积（DVs）与Logan图之间存在良好的关系。其中，丘脑最高，脑桥、小脑、基底节区中等，大脑皮层较低。DV值与体外人脑nAChR密度自显影实验结果吻合较好。吸烟状态下的DV明显低于无烟状态。与对照组相比，PD组在所有脑区都显示DV减少的趋势，脑干和额叶皮层的DV减少具有统计学意义。虽然年龄、病程、左旋多巴日剂量、PD用药持续时间和统一帕金森病评定量表运动部分评分与任何脑区DVs均无显著相关，但高日剂量多巴胺激动剂与地层、小脑、颞叶和顶叶皮层DVs呈显著负相关。这些发现表明，没有痴呆的PD患者可以表现出大脑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。我们的结果还表明，5IA SPECT可能成为定量测量其他神经退行性疾病nachr的有效方法。少

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