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

Purpose [1134 C]DASB is currently the most frequently applied highly selective radiotracer for visualisation and quantification of central SERT. Its use, however, is hampered by the short half life of carbon-11, the moderate cortical test retest reliability, and the lack for quantifying endogenous serotonin. Labelling with fluorine-18 allows in principle for longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly apply in human the new highly SERT-selective fluorine-18 labelled fluoromethyl analogue of (+)-McN5652 ((+)-[1840 F]FMe-McN5652) and to evaluate its potential for SERT quantification. Methods The PET data of five healthy volunteers (3 male, 2 female, age 39 ± 10 years) coregistered with individual MRI were semi-quantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and distribution volume ratios (DVR) were calculated using a 2-tissue compartment model and arterial input function measurement were corrected for metabolites/plasma data. Standardized uptake region-to-cerebellum ratios as measure of specific radiotracer accumulation were compared with those of a [1146 C]DASB-PET data set of healthy subjects (10 male, 11 female, 38 ± 8 years). Results The 2-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume (VT) demonstrated good identifiability based on coefficient of variation (COV) for the volumes of interest (VOIs) in SERT-rich and also for cortical areas (COV VT < 10%). Compared with [11C]DASB-PET, there was a tendency to lower mean values in (+)-[1851 F]FMe-McN5652 PET, however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[1853 F]FMe-McN5652 uptake corresponds well with the known SERT distribution also in humans. Conclusion The results showed also that (+)-[1855 F]FMe-McN5652 is suitable for in vivo quantification of SERT with PET. Because of the long half