Song Jia, Peng Xiaohui, Li Linlin, Yang Fan, Zhang Xiaojun, Zhang Jinming, Dai Jiapei, Cui Mengchao
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing 100853, P. R. China.
ACS Omega. 2018 Oct 31;3(10):13089-13096. doi: 10.1021/acsomega.8b01120. Epub 2018 Oct 12.
In this study, we synthesized four novel AlF-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to Aβ aggregates, of which complex possessing the most potent affinity ( = 11.3 nM) was selected for further biological evaluations. In vitro fluorescent staining and in vitro autoradiography studies on brain sections from CAA patients proved that this ligand could label Aβ deposits in blood vessels selectively. In biodistribution study, [F] can hardly penetrate the blood-brain barrier (brain = 0.3% ID/g) and displayed a rapid blood washout rate (blood/blood = 25.2), which is favorable as CAA imaging agents. In conclusion, this AlF-labeled 2-phenylbenzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent.
在本研究中，我们通过烷基连接体合成了四种新型的与1,4,7-三氮杂环壬烷-1,4-二乙酸共轭的AlF标记的2-苯基苯并噻唑衍生物，并将它们评估为针对沉积在脑淀粉样血管病（CAA）大脑血管中的淀粉样β（Aβ）斑块的成像剂靶点。这四种配体对Aβ聚集体表现出中等到高的结合能力，其中具有最强亲和力（Kd = 11.3 nM）的配合物被选作进一步的生物学评估。对CAA患者脑切片进行的体外荧光染色和体外放射自显影研究证明，该配体能够选择性地标记血管中的Aβ沉积物。在生物分布研究中，[F]几乎无法穿透血脑屏障（脑摄取率 = 0.3% ID/g），并显示出快速的血液清除率（血液/血液 = 25.2），这作为CAA成像剂是有利的。总之，这种AlF标记的2-苯基苯并噻唑配合物被开发出来，并被证明是一种有前景的CAA正电子发射断层显像剂。
