The evaluation of nicotinic acetylcholine receptors in patients with neurodegenerative disorders

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，并应用于神经退行性疾病的研究，在健康志愿者中，于注射I-123 5IA后立即进行6 h动态SPECT采集。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。对吸烟健康志愿者进行两次扫描，一次在吸烟状态下，另一次在戒烟20天后。我们还对Alzheimer病（AD）和帕金森病（PD）患者进行了5IA SPECT检查，用2C和Logan图得到的两个分布容积（DV）之间有良好的相关性。DVs以丘脑最高，脑桥、小脑、基底节次之，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。AD患者各脑区DV值均较正常对照组显著降低。丘脑和脑桥PD的DVs明显降低。运动不能型PD患者几乎所有脑区的DVs均显著降低，而震颤型PD患者仅丘脑DVs显著降低，这可能与抗胆碱能药物治疗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.