(AlF)-F-18-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy

作者：Song, Jia; Peng, Xiaohui; Li, Linlin; Yang, Fan; Zhang, Xiaojun; Zhang, Jinming^*; Dai, Jiapei; Cui, Mengchao^*

来源：ACS Omega, 2018, 3(10): 13089-13096.

DOI：10.1021/acsomega.8b01120

• PITTSBURGH COMPOUND B
• ALZHEIMERS-DISEASE
• COGNITIVE IMPAIRMENT
• BETA PLAQUES
• BRAIN
• COMPLEXES
• ALUMINUM
• FLUORIDE
• PET
• MECHANISM

In this study, we synthesized four novel (AlF)-F-18/19-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-beta (N beta) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to A beta(1-42) aggregates, of which complex 17 possessing the most potent affinity (K-i = 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 A beta deposits in blood vessels selectively. In biodistribution study, [F-18] 17 can hardly penetrate the blood-brain barrier (brain(2) (min) = 0.3% ID/g) and displayed a rapid blood washout rate (blood(2 min)/blood(60 min) = 25.2), which is favorable as CAA imaging agents. In conclusion, this (AlF)-F-18-labeled 2-phenyffienzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent.

• 出版日期2018-10
• 单位中国人民解放军总医院; 北京师范大学; 中南民族大学