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Abstract: An improved synthesis of N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2-(2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[18F]/K2.2.2 at 120°C followed by reduction with BH3 at 80°C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7±2.4% (n=6) and 14.8±4.0% (n=5), respectively, in a synthesis time of 120min from EOB. The specific activity of 2 was 3Ci/μmol or 111GBq/μmol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[18F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron. [Copyright &y& Elsevier]

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]/K2.2.2 followed by reduction with NaBH4/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 120min and the specific activity was 1.75±0.77Ci/μmol (n=13, EOS). The 4-[18F]-ADAM synthesized by this module was stable over 4h at room temperature and is suitable for imaging SERT in humans. [Copyright &y& Elsevier]