(18)F-Mefway PET Imaging of Serotonin 1A Receptors in Humans: A Comparison with (18)F-FCWAY

INTRODUCTION: The purpose of this research is to evaluate the prospects for the use of 4-(trans-(18)F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide ((18)F-Mefway) in comparison to (18)F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide ((18)F-FCWAY) for the quantification of 5-HT(1A) receptors in human subjects. METHOD: Five healthy male controls were included for two positron emission tomography (PET) studies: (18)F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, (18)F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio). RESULT: Although the pattern of regional uptakes in the (18)F-Mefway PET was similar to that of the (18)F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in (18)F-Mefway PET was almost half of that in (18)F-FCWAY PET. The skull uptake in (18)F-Mefway PET was only 25% of that in (18)F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for (18)F-Mefway were 17—40% lower than those of (18)F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in (18)F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in (18)F-Mefway PET. CONCLUSION: As (18)F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, (18)F-Mefway may appear less favorable than (18)F-FCWAY. However, in contrast to (18)F-FCWAY, the resistance to in vivo defluorination of (18)F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, (18)F-Mefway may be a good candidate PET radioligand for 5-HT(1A) receptor imaging in human.