Charles A. Alt

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

[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. 11CH3I was bubbled into a solution of S-(+)-N-methyl-alpha-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 degrees C for 8 min. [11C]Dapoxetine.HCl was purified by HPLC on a C18 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/mumol [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.