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

RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE

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

CHEN Zhengping，

LIU Chunyi，

LI xiaomin，

TANG Jie，

TAN Cheng，

HUANG Hongbo，

YU Huixin，

LUO Shineng

Nuclear Science and Techniques

Vol.23, No.1

pp.40-46

Published in print 20 Feb 2012

DOI：10.13538/j.1001-8042/nst.23.40-46

31200

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 60 min 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 80–120 min. 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.

VMAT2, Imaging agent18F-FP-DTBZSynthesisBiodistributionMicroPETParkinson's disease

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