Novel Cyclopentadienyl Tricarbonyl Complexes of 99mTc Mimicking Chalcone as Potential Single-Photon Emission Computed Tomography Imaging Probes for 尾-Amyloid Plaques in Brain

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• 作者：Zijing Li ; Mengchao Cui ; Jiapei Dai ; Xuedan Wang ; Pingrong Yu ; Yanping Yang ; Jianhua Jia ; Hualong Fu ; Masahiro Ono ; Hongmei Jia ; Hideo Saji ; Boli Liu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：January 24, 2013
• 年：2013
• 卷：56
• 期：2
• 页码：471-482
• 全文大小：567K
• 年卷期：v.56,no.2(January 24, 2013)
• ISSN：1520-4804

文摘

Rhenium and technetium-99m cyclopentadienyl tricarbonyl complexes mimicking the chalcone structure were prepared. These complexes were proved to have affinity to 尾-amyloid (A尾) in fluorescent staining on brain sections of Alzheimer鈥檚 Disease (AD) patient and binding assay using A尾_1鈥?2 aggregates, with K_i values ranging from 899 to 108 nM as the extension of conjugated 蟺 system. In vitro autoradiograpy on sections of transgenic mouse brain confirmed the affinity of [^99mTc]5 (K_i = 108 nM). In biodistribution, all compounds showed good initial uptakes into the brain and fast blood clearance, while the decreasing of initial brain uptakes correspond to increasing of conjugation length, from 4.10 卤 0.38% ID/g ([^99mTc]3) to 1.11 卤 0.34% ID/g ([^99mTc]5). These small technetium-99m complexes (<500 Da) designed by an integrated approach provide encouraging evidence that development of a promising ^99mTc-labeled agent for imaging A尾 plaques in the brain may be feasible.