Semi-automated synthesis,validation and microPET imaging of ^(18)F-FP-DTBZ as a vesicular monoamine transporter ligand

查看全文 作　　者：CHEN [1]Zhengping;LIU [1]Chunyi;LI [1]xiaomin;TANG [1]Jie;TAN [1]Cheng;HUANG [1]Hongbo;YU [1]Huixin;LUO [1]Shineng 机构地区：[1]Key Laboratory of Nuclear Medicine,Ministry of Health,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China 出　　处：《Nuclear Science and Techniques》索引2012年第23卷第1期,共7页 基　　金：Supported by the National Natural Science Foundation of China (30970844);the Outstanding Medical Professionals Foundation of Jiangsu Province (RC2011096);Natural Science Foundation of Jiangsu Province of China (BK2010155) 摘　　要：This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by a semi-automated procedure in a 21-35% yield without decay correction and with a radiochemical purity of >98%.Bioistribution in rats exhibited a favorable brain uptakes of the ligand (0.31±0.04 ID% at 60min post injection,n=8).The highest radioactivity located in VMAT2 enriched striatal tissue.The target-to-nontarget ratio (striatum/cerebellum,ST/CB) was 4.81±0.84.Blocking studies implied that striatum uptake could be blocked by DTBZ (a VMAT2 inhibitor) but could not by CFT (a dopamine transporter inhibitor).MicroPET imaging with 18F-FP-DTBZ in normal rats gave high quality images in which high radioactivity were observed in the striatal tissue.Time-and-activity curves revealed good retention in the target (striatum) and rapid clearance in the background (cerebellum),which resulted in a maximum ST/CB ratio of 5.08±0.81 (n=3) in 80-120min.By contrast,the 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18F-FP-DTBZ concentration on the unlesioned side (unlesioned-ST/CB=5.21±0.38,n=3) than the lesioned (lesioned-ST/CB=2.34±0.51).The results validated that 18F-FP-DTBZ is a favorable PET ligand binding to VMAT2. 关 键 词：半自动化 转运蛋白 成像质量 合成 验证 单胺 囊泡 放射化学纯度