99mTc(CO)3-Labeled Benzothiazole Derivatives Preferentially Bind Cerebrovascular Amyloid: Potential Use as Imaging Agents for Cerebral Amyloid Angiopathy

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• 作者：Jianhua Jia ; Mengchao Cui ; Jiapei Dai ; Boli Liu
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：August 3, 2015
• 年：2015
• 卷：12
• 期：8
• 页码：2937-2946
• 全文大小：742K
• ISSN：1543-8392

文摘

Cerebral amyloid angiopathy (CAA) is a disorder affecting the elderly that is characterized by amyloid-尾 (A尾) deposition in blood vessel walls of the brain. A series of ^99mTc(CO)₃-labeled benzothiazole derivatives as potential SPECT imaging probes for cerebrovascular A尾 deposition is reported. Rhenium surrogate displayed high affinities to A尾 aggregates with K_i values ranging from 106 to 42 nM, and they strongly stained A尾 deposits in transgenic mice (Tg) and Alzheimer鈥檚 disease (AD) patients. In vitro autoradiography on brain sections of Tg and AD patients confirmed that [^99mTc]24 possessed sufficient affinity for A尾 plaques, and [^99mTc]24 could only label A尾 deposition in blood vessels but not A尾 plaques in the parenchyma of the brain of AD patients. Moreover, [^99mTc]24 possessed favorable initial uptake (1.21% ID/g) and fast blood washout (blood_{2 min}/blood_{60 min} = 23) in normal mice. These preliminary results suggest that [^99mTc]24 may be used as an A尾 imaging probe for the detection of CAA.