Structural requirement of C11b chirality of tetrabenazine analogs as VMAT2 imaging ligands: synthesis and in vivo evaluation期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Structural requirement of C11b chirality of tetrabenazine analogs as VMAT2 imaging ligands: synthesis and in vivo evaluation

Authors:	Danlu Xue Chunyi Liu Xiaomin Li Jie Tang Lihua Cao Yi Liu Zhengping Chen

Affiliation:	1.Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi,China;2.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,Xuzhou Medical University,Xuzhou,China

Abstract:	We studied on the structural requirement of C11b chirality of tetrabenazine (TBZ) analogs as vesicular monoamine transporter 2 (VMAT2) ligands. TBZ analogs (2, 6a, 6b) and ¹⁸F-radiolabeled [¹⁸F]6a and [¹⁸F]6b with eliminated C11b chirality were synthesized and characterized. Competition studies demonstrated that 2, 6a and 6b displayed much lower in vivo VMAT2 bindings than TBZ. MicroPET imaging studies of [¹⁸F]6a and [¹⁸F]6b showed negligible accumulation in VMAT2-enriched regions as compared with the known VMAT2 ligand ¹⁸F-FP-(+)-DTBZ. These results suggest that C11b chirality of TBZ analogs is essential for in vivo VMAT2 binding bioactivity.

Keywords:
本文献已被 SpringerLink 等数据库收录！