An automated synthesis of N, N-dimethyl-2-(2-amino-4-[ 18F]fluorophenylthio)benzylamine (4-[ 18F]-ADAM) for imaging serotonin transporters

Abstract

N,N-dimethyl-2-(2-amino-4-[ 18F]fluorophenylthio)benzylamine (4-[ 18F]-ADAM, 3) is a potent serotonin transporter (SERT) imaging agent. In order to fulfill the demand of pre-clinical studies, we have developed an automated synthesis unit to synthesize this radioligand. The 4-[ 18F]-ADAM was synthesized using TracerLab FN and FE modules and a modified module control program (TracerLab-Fx). The synthesis sequences were similar to that of the manual synthesis, i.e. nucleophilic fluorination of N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine ( 1) with K[ 18F]/K 2.2.2 followed by reduction with NaBH 4/Cu(OAc) 2 and purifications with high-performance liquid chromatography (HPLC) and solid phase extraction. The radiochemical yield of 3 was 1.5±0.3% ( n=13, EOS). The synthesis time was 120 min and the specific activity was 1.75±0.77 Ci/μmol ( n=13, EOS). The 4-[ 18F]-ADAM synthesized by this module was stable over 4 h at room temperature and is suitable for imaging SERT in humans.