Huan Wang, Aiqin Wu, Jianping Liu, Qianqian Xue, Xia Lu, Lei Yin, Yu Fang, Huabei Zhang
aKey Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University bDepartment of Nuclear Medicine, Beijing An Zhen Hospital of the Capital University of Medical Sciences cDepartment of Nuclear Medicine, Peking University First Hospital, Beijing, People's Republic of China.
Nucl Med Commun. 2017 Aug;38(8):683-693. doi: 10.1097/MNM.0000000000000700.
The aim of this study was to develop several novel α7-nicotinic acetylcholine receptor (nAChR) radioligands for the early diagnosis and treatment of Alzheimer's disease.
The study reported six compounds and studied the in-vitro receptor binding affinity, and selected the I-labeled IBT with good characteristics as a novel radioligand suitable for studying α7-nAChRs. After verifying the stability of the radiotracer [I]IBT, the biodistribution in vivo and regional brain biodistribution studies were carried out in mice. Blocking studies with methyllycaconitine citrate and nicotine were carried out under control and blocking conditions, and the metabolic stability was assessed in vivo in the plasma, brain, and liver.
The results of our study suggested that [I]IBT had affinity for α7-nAChRs. The in-vivo evaluation in mice of [I]IBT showed a high brain/blood ratio and excellent metabolic stability. The regional brain distribution studies and the blocking studies showed that it had favorable selectivity and specificity and was a potential α7-nAChRs radioligand.
本研究旨在开发几种新型α7-烟碱型乙酰胆碱受体（nAChR）放射性配体，用于阿尔茨海默病的早期诊断和治疗。
该研究报告了六种化合物，并研究了它们的体外受体结合亲和力，选择具有良好特性的I标记的IBT作为适合研究α7-nAChRs的新型放射性配体。在验证放射性示踪剂[I]IBT的稳定性后，在小鼠体内进行了生物分布和脑区生物分布研究。在对照和阻断条件下用柠檬酸甲基乌头碱和尼古丁进行阻断研究，并在体内评估血浆、脑和肝脏中的代谢稳定性。
我们的研究结果表明，[I]IBT对α7-nAChRs具有亲和力。对[I]IBT在小鼠体内的评估显示出高脑/血比和优异的代谢稳定性。脑区分布研究和阻断研究表明，它具有良好的选择性和特异性，是一种潜在的α7-nAChRs放射性配体。
