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

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.

This work was to develop a semi-automated synthesis of lSF-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 postinjection, 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 （striaturn） 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 rain. By contrast, the6-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.