Comparative assessment of 18F‐Mefway as a serotonin 5‐HT1A receptor PET imaging agent across species: Rodents, nonhuman primates, and humans. Issue 7 (18th November 2015)

• Record Type: Journal Article
• Authors: Mukherjee, Jogeshwar; Bajwa, Alisha K.; Wooten, Dustin W.; Hillmer, Ansel T.; Pan, Min‐Liang; Pandey, Suresh K.; Saigal, Neil; Christian, Bradley T.
• Is Part Of: Journal of comparative neurology. Volume 524:Issue 7(2016)
• Page Start: 1457
• Page End: 1471
• Publication Date: 2015-11-18
• Subjects: raphe nucleus -- hippocampus -- translational research -- receptor selectivity -- P‐glycoprotein; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.23919
• Languages: English
• ISSNs: 0021-9967

Abstract

ABSTRACT: We have developed 18 F‐ trans ‐Mefway ( 18 F‐Mefway) for positron emission tomography (PET) imaging studies of serotonin 5‐HT1A receptors which are implicated in various brain functions. Translation of imaging the 5‐HT1A receptor in animal models to humans will facilitate an understanding of the role of the receptor in human brain disorders. We report comparative brain distribution of 18 F‐Mefway in normal mice, rats, monkeys, and healthy human volunteers. Mefway was found to be very selective, with subnanomolar affinity for the 5‐HT1A receptor. Affinities of >55 nM were found for all other human‐cloned receptor subtypes tested. Mefway was found to be a poor substrate (>30 μM) for the multidrug resistance 1 protein, suggesting low likelihood of brain uptake being affected by P‐glycoprotein. Cerebellum was used as a reference region in all imaging studies across all species due to the low levels of 18 F‐Mefway binding. Consistent binding of 18 F‐Mefway in cortical regions, hippocampus, and raphe was observed across all species. 18 F‐Mefway in the human brain regions correlated with the known postmortem distribution of 5‐HT1A receptors. Quantitation of raphe was affected by the resolution of the PET scanners in rodents, whereas monkeys and humans showed a raphe to cerebellum ratio of approximately 3. 18 F‐Mefway appears to be an effective 5‐HT1A receptor imaging agent in all models, including humans. 18 F‐Mefway therefore may be used to quantify 5‐HT1A receptor distribution in brain regions for the study of various CNS disorders. J. Comp. Neurol. 524:1457–1471, 2016. © 2015 Wiley Periodicals, Inc. Abstract : We have developed 18 F‐ trans ‐Mefway ( 18 F‐Mefway) for PET imaging studies of 5‐HT1A receptors. We report comparative brain distribution of 18 F‐mefway in normal mice, rats, monkeys, and healthy human volunteers. Translation of imaging the 5‐HT1A receptor in animal models to humans will facilitate an understanding of the role of the receptor in human brain disorders.