[en] The present study describes the synthesis of the [¹⁸F]fluoromethyl analogue of (+)-McN5652 ([¹⁸F]FMe-McN) as a new potential tracer for the serotonin transporter. In vitro binding studies have shown that FMe-McN displays only slightly lower affinity for the serotonin transporter (K_i=2.3±0.1 nM) than (+)-McN5652 (K_i=0.72±0.2 nM). The radiofluorinated tracer [¹⁸F]FMe-McN was prepared by reaction of normethyl (+)-McN5652 with the fluoromethylation agent [¹⁸F]bromofluoromethane in an overall radiochemical yield of 5 ± 1% (decay-corrected, related to [¹⁸F]fluoride) and with high specific radioactivity (200-2,000 GBq/μmol at the end of synthesis)

[en] N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (S Me-Adam, 1) is a highly potent and selective inhibitor of the serotonin transporter (SPERT). 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]S Me-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 SPERT, 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

[en] [¹¹C]DASB is currently the most frequently used highly selective radiotracer for visualization and quantification of central SERT. Its use, however, is hampered by the short half-life of ¹¹C, the moderate cortical test-retest reliability, and the lack of quantifying endogenous serotonin. Labelling with ¹⁸F allows in principle longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly use the new highly SERT-selective ¹⁸F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[¹⁸F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification. The PET data from five healthy volunteers (three men, two women, age 39 ± 10 years) coregistered with individual MRI scans were semiquantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and total distribution volumes (V_T) were calculated using a two-tissue compartment model and arterial input function measurements were corrected for metabolite/plasma data. Standardized uptake region-to-cerebellum ratios as a measure of specific radiotracer accumulation were compared with those of a [¹¹C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years). The two-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume (V_T) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V_T <10%). Compared with [¹¹C]DASB PET, there was a tendency to lower mean uptake values in (+)-[¹⁸F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[¹⁸F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans. The results showed that (+)-[¹⁸F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of ¹⁸F, the widespread use within a satellite concept seems feasible. (orig.)