Synthesis and biological evaluation of 1-(4-(4-(4-[18F]fluorobenzyl)-1-piperazinyl)butyl)indolin-2-one as dopamine D4 receptor ligand

A potential dopamine D₄ receptor ligand, 1-(4-(4-(4-fluorobenzyl)-1-piperazinyl)butyl)indolin-2-one (4) was synthesized through a four-step process and its affinity and selectivity for dopamine D₂-like receptors was determined through in vitro receptor binding assay. ¹⁸F]4 was prepared using a one-pot two-step method with total radiochemical yield 21.2 % (decay-corrected). The molar radioactivity was around 135 GBq/μmol and the radiochemical purity was greater than 95.5 %. The partition coefficient (Log P) of ¹⁸F]4 was determined to be 2.10 ± 0.30 through octanol experiment. The in vivo biodistribution and the competitive distribution of ¹⁸F]4 in rat exposed that the tracer passes through blood–brain-barrier (BBB) and may specifically bind to D₄ receptor. Metabolite analysis revealed that there was no metabolism of ¹⁸F]4 in brain. Conclusively, these preliminary results demonstrated that ¹⁸F]4 shows promises as a radioligand for the in vivo study of dopamine D₄ receptor.