Imaging of the brain serotonin transporters (SERT) with ^sup 18^F-labelled fluoromethyl-McN5652 and PET in humans

[^sup 11^C]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 ^sup 11^C, the moderate cortical test-retest reliability, and the lack of quantifying endogenous serotonin. Labelling with ^sup 18^F 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 ^sup 18^F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[^sup 18^F]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 ^sub 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 [^sup 11^C]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 ^sub T^) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V ^sub T^