Synthesis and biological evaluation of 3-{[4-(4-[18F]fluorophenyl)methyl] piperazin-1-yl}-methyl-1H-pyrrolo[2,3-b]pyridine for in vivo studies of dopamine D4 receptor

The compound 3-{[4-(4-[F-18]fluorophenyl)methyl]piperazin-1-yl}-methyl-1H-pyrrolo[2,3-b]pyridine ([F-18]3), which is an analogue of L-745,870 binding D-4 receptor in vitro was synthesized and evaluated. The compound [F-18] 3 was prepared by reductive alkylation of 3-(piperazin-1-yl)methyl-1H-pyrrolo[2,3-b]pyridine (2) with 4-[F-18]fluorobenzaldehyde with a radiochemical yield of 9.0-12.0% (decay-corrected) and high specific activity (>37 GBq/mumol). Tissue distribution and metabolism studies in rats demonstrated the specific distribution of [F-18] 3 in brain regions, suggesting that this radioligand may be a suitable PET trace agent for in vivo studies of dopamine D-4 receptor.