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

Abstract 

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [¹¹C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [¹¹C]SMe-ADAM. The 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). The specific uptake reached a thalamus to cerebellum ratio of 6.74±0.95 at 60 min postinjection. The [¹¹C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38±11% of the control value. 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.

Keywords: [¹¹C]SMe-ADAM, Serotonin transporter, [¹¹C]Methyl iodide, MicroPET