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

神经型烟碱型乙酰胆碱受体(NAChRs)广泛分布于人脑。最近合成了5-碘-3-(2S)-氮杂二乙基甲氧基)吡啶(5IA)作为放射性配体，用于核受体的SPECT显像。本研究的目的是用5IA SPECT建立nAChR结合的定量测量，并将其应用于帕金森病患者。在健康志愿者中，在注射I-123 5IA后立即进行6h动态SPECT采集。采集动脉血，用薄层层析法作为输入函数，得到纯5IA浓度。采用二房室模型(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，另一次是戒烟20天后。在第二项研究中，我们对帕金森病(PD)患者进行了5IA SPECT研究，用2C和Logan图得到的分布体积(DV)之间有很好的相关性。DVD是TH…丘脑最高，桥脑、小脑、基底节次之，大脑皮层较低。人脑组织nAChR密度的DV值与体外放射自显影实验结果吻合较好。吸烟状态下的DV显著低于无烟组。与对照组相比，PD组各脑区DV均有下降趋势，脑干和额叶皮质DV下降有统计学意义。虽然年龄、病程、左旋多巴的日剂量、帕金森病联合评定量表的运动部分评分与任何脑区的DV均无显著相关性，但每日大剂量的多巴胺激动剂与大脑皮质、小脑、颞叶和顶叶皮质的DVS呈显著负相关。这些结果表明，无痴呆的PD患者脑内nAChRs减少，尤其是在脑干和额叶皮质。他们还表明，多巴胺激动剂可能会对nAChRs的分布产生负面影响。我们的结果还表明，5IA SPECT可能成为其他神经退行性疾病中nAChRs定量测量的有用方法。较少

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