First-in-human trial of new serotonin receptor agent

F-18 mefway is a novel serotonin-1A receptor ligand that could one day be used to image neurodegenerative disease and psychiatric disorders, according to a story published Nov. 13 in the Journal of Nuclear Medicine.

Other agents have been used in this capacity, namely C-11 WAY-100635, but dependence on an on-site cyclotron and the very short half-life of carbon-11 agents renders it inconvenient to use, despite its clinical value, wrote Ansel T. Hillmer, PhD, from the department of medical physics at the University of Wisconsin in Madison, and colleagues.

Researchers have been developing fluorine-18 based analogs of WAY-100635, such as F-18 MPPF and F-18 FCWAY, but the former is associated with inadequate penetration into the brain and the latter with unwanted bone uptake.

F-18 mefway, an acronym for an impossibly long chemical name, showed improved stability in preclinical studies and comparable pharmacokinetics to WAY-100635 binding in serotonin-1A (5-HT1A) receptors.

“F-18 mefway possesses a simple radiochemical production, brain uptake levels comparable to other 5-HT1A radioligands, a high signal-to-noise ratio, suitable kinetic properties, no apparent PET signal in bone, and higher detected nonspecific PET signal than C-11 radioligands, making it a promising candidate for imaging 5-HT1A receptors in humans,” wrote the researchers.

For this study, two men and four women between the ages of 22 and 38 underwent F-18 mefway PET and MR imaging. Results indicated good distribution of the agent among 5-HT1A receptors with strong regional binding potential values shown in the areas of the mesial temporal lobe (measured at 2.4), the insular cortex (1.6), and in various cortical regions (0.7-1.0).

“Future studies to assess the viability of F-18 mefway in pathology-specific populations are merited,” concluded Hillmer et al.