First In-Human Data of Fluorine-18 Labelled Fluoromethyl-McN5652 for In-Vivo imaging of Brain Serotonin Transporters (SERT) with PET

Aim: 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. The aim of our study was to first apply in human the new highly SERT‐selective fluorine‐18 labelled fluoromethyl analogue of (+)‐McN5652 ([18F]FMe‐McN).
Methods: The synthesis of [18F]FMe‐McN was performed according to Zessin et al. with some modifications. Briefly, the demethylated (+)‐McN5652 was reacted with bromo‐[18F]fluoromethane to yield [18F]FMe‐McN, which was purified by reversed‐phase HPLC. For in vivo human studies, five healthy volunteers (2 female, age 39±10 years) underwent dynamic PET over 120 minutes after intravenuous injection of a 90 s bolus of 298±57 MBq [18F]FMe‐McN and a static acquisition over 30 minutes 3 h p.i.. PET data were coregistered with individual MRI data set using PMOD and VOI analysis was performed. Target‐to‐background‐ratios (TB‐R, cerebellum as background structure) were compared with those of a reference data set assessed by [11C]DASB‐PET in 21 healthy subjects (11 female, 38±8 years).
Results: TB‐R ([18F]FMe‐McN) displays no hemispheric differences. The values are for the frontal cortex (FC) 1.02±0.04 (right‐hand side) and 1.01±0.03 (left), for the head of caudate region (caud) 1.46±0.16 (right) and 1.50±0.15 (left) and for the raphé region 2.04±0.11. Corresponding TB‐R ([11C]DASB) are 1.10±0.07 (FC right, ANOVA p=0.05), 1.08±0.78 (FC left, 0.06), 2.14±0.21 (caud right, 0.02), 2.06±0.19 (caud left, 0.04) und 2.23±0.39 (raphé, 0.04). Visually, image quality of [11C]DASB‐PET is superior to [18F]FMe‐McN .
Conclusion: Cerebral radiotracer uptake fits well with the known SERT distribution also in humans. Hence, [18F]FMe‐McN might be suitable for in vivo quantification of SERT. Despite a tendency to lower TB‐R compared to [11C]DASB, the lower standard deviation of [18F]FMe‐McN TB‐R can be advantageous with regard to test‐retest estimations in larger study cohorts. Also, labelling with fluorine‐18 allows (1) later data acquisition times, which is useful for the investigation of the
tracer kinetics in brain tissue (modelling), and (2) a widespread application within a satellite concept e.g. in multicenter trials.
References Zessin J, Eskola O, Brust P et al. Nucl Med Biol 2001; 28: 857‐863.