Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[18F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D4 receptor radioligand

The dopamine D-4 receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D-4 receptor may be useful to understand the function of the D-4 receptor and its correlations with various disorders. 2-(3-(4-(4-[F-18]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([F-18]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/mu mol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D-2-like receptors were measured through in vitro receptor binding evaluation and the K-i value for the D-4 receptor was determined to be 2.9 +/- 0.2 nM, and its selectivity for the dopamine D-4 receptor is 709-fold versus D-2long receptor, 823-fold versus D-3 receptor. The partition coefficient (Log D) of it was determined to be 2.6 +/- 0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D-4 receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D-4 receptor.