Synthesis of [ 11C]dapoxetine · HCl, a serotonin re-uptake inhibitor: Biodistribution in rat and preliminary PET imaging in the monkey

Abstract

[ 11C]Dapoxetine · HCl, S-( + )- N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was prepared from its mono-methyl precursor, S-( + )- N-methyl-a-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride. Biodistribution was determined in rats at 5, 30 and 60 min after injection and preliminary PET studies were performed in a Rhesus monkey. 11CH 3I was bubbled into a solution of S-( + )- N-methyl-α-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 °C for 8 min. [ 11C]Dapoxetine · HCl was purified by HPLC on a C 18 cartridge eluted with MeOH:phosphate buffer, pH 7.2 (75:25) with a 10% yield (end of synthesis). The time required for the synthesis was 40 min, from the end of bombardment. Radiochemical purity of the final product was >99% and specific activity was routinely >400 mCi/μmol [EOS]. In the biodistribution studies the highest concentration (%ID/g ± SEM) of dapoxetine · HCl was detected in lung: 4.56 ± 0.27 (5 min), 1.28 ± 0.18 (30 min) and 0.67 ± 0.04 (60 min). Brain accumulation was 0.76 ± 0.02 (5 min), 0.46 ± 0.04 (30 min) and 0.27 ± 0.01 (60 min). Preliminary PET studies demonstrated significant displaceable binding in the cerebral cortex and subcortical grey matter. These results demonstrate that [ 11C]dapoxetine · HCl can be prepared in high purity and may be useful for the in vivo evaluation of serotonin re-uptake mechanisms.