Characterization of 4-[ ¹⁸F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: A dynamic study

Introduction: Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4- ¹⁸F-fluorophenylthio)benzylamine (4-[ ¹⁸F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods: Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[ ¹⁸F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[ ¹⁸F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[ ¹⁸F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results: The distribution of 4-[ ¹⁸F]-ADAM reached equilibrium 120-150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120-150 min after 4-[ ¹⁸F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75-2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[ ¹⁸F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion: 4-[ ¹⁸F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.