Mamede Marcelo, Ishizu Koichi, Ueda Masashi, Mukai Takahiro, Iida Yasuhiko, Fukuyama Hidenao, Saga Tsuneo, Saji Hideo
Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Nucl Med. 2004 Sep;45(9):1458-70.
Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain, especially the alpha4beta2 subtype of nAChR. The cholinergic systems have roles in various neurophysiologic functions, such as learning, memory, and cognition, whereas normal aging and neurodegenerative diseases have been associated with changes in nAChRs. Recently, 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. 123I-5IA shows higher affinity toward the nAChR alpha4beta2 subtype, enhanced receptor subtype selectivity, good safety, and low nonspecific binding.
In this study, a SPECT quantitative study of human nAChRs binding with 123I-5IA was conducted in healthy volunteers. An arterial input function was obtained for each subject and a 2-compartment model was used to determine the kinetic parameters of 123I-5IA using data from a 6-h scan. The distribution volume (VT (mL/mL), which is related to the number of unoccupied binding sites in the brain, was calculated and values were compared with results of a graphical analysis (Logan plot, VLG).
Analysis of the unmetabolized compound showed a high parent fraction of 123I-5IA in plasma. The results from the 2-compartment model analysis showed high VT values for the thalamus; moderate values for the brain stem, cerebellum, and basal ganglia; and low values for the cortical regions. Good agreement was observed between VT values and results of autoradiographic experiments done in vitro for nAChR density in human brain. A high correlation index was observed between distribution volumes from model and graphical analyses.
Our results indicated that 123I-5IA SPECT is suitable for the quantification of nAChRs in human brain.
神经元烟碱型乙酰胆碱受体（nAChRs）广泛分布于人类大脑中，尤其是nAChR的α4β2亚型。胆碱能系统在多种神经生理功能中发挥作用，如学习、记忆和认知，而正常衰老和神经退行性疾病与nAChRs的变化有关。最近，已合成5-碘-3-(2(S)-氮杂环丁烷甲氧基)吡啶（5IA）作为用单光子发射计算机断层扫描（SPECT）成像nAChRs的放射性配体。123I-5IA对nAChRα4β2亚型显示出更高的亲和力、增强的受体亚型选择性、良好的安全性和低非特异性结合。
在本研究中，对健康志愿者进行了用123I-5IA结合人nAChRs的SPECT定量研究。为每个受试者获取动脉输入函数，并使用两室模型根据6小时扫描的数据确定123I-5IA的动力学参数。计算分布容积（VT，mL/mL，与脑中未占据结合位点的数量相关），并将值与图形分析（洛根图，VLG）的结果进行比较。
对未代谢化合物的分析显示，123I-5IA在血浆中的母体分数很高。两室模型分析的结果显示，丘脑的VT值高；脑干、小脑和基底神经节的值中等；皮质区域的值低。在VT值与体外对人脑nAChR密度进行的放射自显影实验结果之间观察到良好的一致性。在模型分析和图形分析的分布容积之间观察到高相关指数。
我们的结果表明，123I-5IA SPECT适用于定量人脑nAChRs。
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