Synthesis and comparison of 4-[18F]F-ADAM, 2-[18F]F-ADAM, N-Desmethyl-4-[18F]F-ADAM and [18F]F-AFM as serotonin transporter imaging agents

4-[18F]F-ADAM (1a), 2-[18F]F-ADAM (2a), N-Desmethyl-4-[18F]F-ADAM (3a) and [18F]F-AFM (4a ) were synthesized in 1.7, 3.9, 2.9 and 0.6% yield (EOS), respectively, in a synthesis time of ∼120 min from EOB. PET studies in rats showed that the maximum specific uptake ratios of 1a, 2a, 3a and 4a in midbrain were 3.86, 0.73, 0.35 and 2.23, respectively. Thus, in terms of radiochemical yield, specific binding and in vivo stability, 4-[18F]F-ADAM may be the most appropriate SERT imaging agent for human studies. - Highlights: ► Four 18F-labeled radioligands were synthesized and evaluated as SERT imaging agents. ► 4-[18F]F-ADAM and [18F]F-AFM had high specific uptake in SERT-rich brain regions. ► 2-[18F]F-ADAM and N-Desmethyl-4-[18F]F-ADAM had low specific uptake in brain. ► 4-[18F]F-ADAM may be the most appropriate SERT imaging agent for human studies.