The evaluation of nicotinic acetylcholine receptors in patients with neurodegenerative disorders

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，并将其应用于神经退行性疾病。健康志愿者在注射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。我们还对阿尔茨海默病(AD)和帕金森病(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。DVS以丘脑最高，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。AD患者各脑区的DV值均显著低于正常对照组。帕金森病患者丘脑和脑桥的DV明显降低。运动迟缓型帕金森病患者几乎所有脑区的DV均显著降低，而震颤型PD患者仅丘脑DV明显降低，这可能与抗胆碱能药物对PD症状的疗效有关。

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 neurodegenerative 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. We also performed 5IA SPECT studies in the patients with Alzheimer's disease (AD) and Parkinson's disease (PD).Good relationship was found between two distribution volumes(DV) obtained by using 2C and Logan plot. DVs were the 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 DV values of AD were significantly reduced in all brain regions in comparison with those of normal controls. The DVs of PD were significantly lowered in the thalamus and the pons. The significant reductions were found in DVs of akinesia dominant PD patients in almost all brain regions, however, only in the thalamus in DVs of tremor dominant patients, which may be related with the efficacy of anti-cholinergic drugs for symptoms of PD.Our results indicated that 5IA SPECT may become a useful method for the quantitative measurements for nAChRs in neurodegenerative disorders.