[¹¹C]SMe-ADAM, an imaging agent for the brain serotonin transporter: Synthesis, pharmacological characterization and microPET studies in rats

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) was found to be a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labelled with carbon-11 by methylation of the S-desmethyl precursor 10 with [¹¹C]methyl iodide to obtain the potential positron emission tomography radiotracer [¹¹C]SMe-ADAM. Radiochemical yield was 27  5 % and the specific radioactivity was 26 – 40 GBq/µmol at the end of synthesis . Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 ± 0.41 %ID/g at 5 min after injection). This is the highest brain uptake ever reported for this type of radiotracer in rats. The specific uptake reached a thalamus to cerebellum ratio of 6.74 ± 0.95 at 60 min post injection. The [¹¹C]SMe-ADAM uptake in the thalamus was significantly decreased by pre-treatment with fluoxetine to 45 ± 9 % of the control values. Furthermore, no metabolites of [¹¹C]SMe-ADAM could be detected in the SERT rich regions of the rat brain. It is concluded that [¹¹C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.