Fully automated one-pot two-step synthesis of 4-[¹⁸F]-ADAM, a potent serotonin transporter imaging agent

Introduction: N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM, 2) is a potent serotonin transporter (SERT) imaging agent. In order to fulfill the demand of clinical studies, we have developed a fully automated one-pot two-step synthesis of this potent SERT imaging agent. Methods: The 4-[¹⁸F]-ADAM (2) was synthesized using a commercially available GE TRACERlab FN module. Briefly, the precursor, N,N-dimethyl-2-(2,4-dinitrophenylthio) benzylamine (1) in DMSO was reacted with K[¹⁸F]/K_2.2.2 in a glassy carbon reaction vessel at 120 °C for 7.5 min followed by reduction of the intermediate with NaBH₄/Cu(OAc)₂ in EtOH in the same vessel at 80 °C for 20 min. The reaction mixture was then purified with high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) to give (2). The quality of (2) synthesized by this method was verified by HPLC and TLC as compared to its authentic sample synthesized by two-pot two-step method. Results: Using this automated one-pot two-step method, the radiochemical yield (RCY) of (2) was 2.5±0.8% (n=12, EOS) in a synthesis time of 100±6 min from EOB with a specific activity of 4.4±1.9 Ci/μmol (n=12, EOS). Radioligand (2) was stable over 4 h at room temperature. Conclusions: This fully automated one-pot two-step synthetic method using a commercially available GE TRACERlab FN module could simplify the synthesis of 4-[¹⁸F]-ADAM (2) and fulfill its demand for both animal and human studies, especially for study sites without a cyclotron. - Highlights: • 4-[¹⁸F]-ADAM (2) was prepared by one-pot two step method with TRACERlab FN module. • The RCY (2) was ~3%, synthesis time was ~100 min and SA was ~5.0 Ci/μmol (EOS). • The concentration of EtOH, ACN and DMSO in (2) were 10, 0.04, 0.5%, respectively. • (2) prepared by this method is suitable for both animals and human studies.