First-in-Human Evaluation of 18F-Mefway, a PET Radioligand Specific to Serotonin-1A Receptors

The serotonin-1A (5-HT1A) receptor is implicated in an array of neurological and psychiatric disorders. Current PET radioligands targeting 5-HT1A receptors have limitations hindering widespread PET studies of this receptor system. The 5-HT1A specific antagonist radioligand N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(trans-4-18F-fluoromethylcyclohexane)carboxamide (18F-mefway) exhibited promising in vivo properties in rhesus monkeys. The goal of this work was to examine the in vivo cerebral binding profile and metabolism of 18F-mefway in humans. Methods Dynamic 18F-mefway PET data were acquired for six healthy volunteers (4F, 2M; 22–38 years). Scans were initiated with the injection of 192–204 MBq radiotracer and data were acquired for two hours. Venous blood samples were collected and assayed to examine the in vivo metabolism profile of 18F-mefway. To examine the test-retest variability of 18F-mefway, a second PET scan was acquired at least two weeks later for four subjects. Regional binding potentials (BPND) were calculated with MRTM, and voxel-wise BPND maps were calculated with Logan graphical analysis. Regions surrounding the brain were carefully inspected for uptake of radiolabeled species in bone.