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

Purpose [ 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 11 C, the moderate cortical test–retest reliability, and the lack of quantifying endogenous serotonin. Labelling with 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 18 F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[ 18 F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification. Methods 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 [ 11 C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years). Results 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 [ 11 C]DASB PET, there was a tendency to lower mean uptake values in (+)-[ 18 F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[ 18 F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans. Conclusion The results showed that (+)-[ 18 F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of 18 F, the widespread use within a satellite concept seems feasible.