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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]

Abstract: Serotonin transporters (SERTs) have been implicated in various neuropsychiatric disorders. We aim to validate 4-[18F]-ADAM (N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine) as a SERT imaging agent in rats using micro-positron emission tomography (micro-PET) and autoradiography. Sixty to ninety min after injecting 4-[18F]-ADAM, specific uptake ratios (SURs) were determined by micro-PET measurements in various brain regions of normal control rats. For n =3, the SUR in the midbrain was 4.94±0.16, for the hypothalamus it was 4.39±0.031 and for the caudate it was 4.18±0.53. The retention of 4-[18F]-ADAM in the hypothalamus and midbrain regions increased rapidly between 5 to 10 min after injection and declined thereafter. The SURs determined by autoradiography were: 9.31±1.41 for the midbrain, 7.15±1.45 for the hypothalamus and 5.22±1.14 for the caudate putamen. Both micro-PET and autoradiography studies revealed a dose-dependent progressive inhibition of radioligand uptake in the frontal cortex, caudate putamen and hypothalamus in rats treated with 0.01 to 0.25 mg/kg paroxetine. A decrease in 4-[18F]-ADAM uptake of approximately 84% was observed in the midbrain of rats pretreated with 0.25 mg/kg paroxetine as compared to controls (4.94±0.16 versus 0.80±0.17, n =3). Both 5,7-dihydroxytryptamine and p-chloroamphetamine-treated rats showed pronounced reduction in 4-[18F]-ADAM binding when compared to normal controls. Rats pretreated with p-chloroamphetamine exhibited significant inhibition of 4-[18F]-ADAM uptake in brain regions rich in SERT over a period of four weeks. Thus, 4-[18F]-ADAM is a SERT-specific radioligand that may be useful for evaluating neuropsychiatric conditions involving serotonergic dysfunction. [Copyright &y& Elsevier]