Synthesis and radiolabeling of N-[4-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide - a potential radiotracer for D3 receptor imaging with PET

FAUC346 (N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), an in vitro D3-selective ligand, and its normethyl derivative have been synthesized from commercially available 1-(2-substituted-phenyl)piperazines. FAUC346 has been labeled using [11C]methyl triflate in acetone containing aqueous NaOH (5 Eq) at −10 °C for 1 min, purified on semipreparative reverse-phase high-performance liquid chromatography (HPLC) and formulated as an intravenous injectable solution using a Sep-Pak Plus C18 device. Up to 5.5 GBq of [11C]FAUC346 (N-[4-[4-(2-[methyl-11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), with a specific radioactivity of 45-75 GBq/μmol, could be obtained in 30-35 min, including HPLC purification and formulation starting from 44.4 GBq of [11C]carbon dioxide. Preliminary pharmacological evaluation of [11C]FAUC346 in rat brain clearly demonstrated in vivo selectivity for D3 receptors and the absence of radiolabeled metabolite within the brain. These encouraging results, however, could not be confirmed in nonhuman primates; therefore, this radioligand does not appear to have the required pharmacological profile for a positron emission tomography probe for imaging D3 receptors.