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Translation of imaging the 5\u2010HT<jats:sub>1A<\/jats:sub> 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 <jats:sup>18<\/jats:sup>F\u2010Mefway in normal mice, rats, monkeys, and healthy human volunteers. Mefway was found to be very selective, with subnanomolar affinity for the 5\u2010HT<jats:sub>1A<\/jats:sub> receptor. Affinities of &gt;55\u2009nM were found for all other human\u2010cloned receptor subtypes tested. Mefway was found to be a poor substrate (&gt;30\u2009\u03bcM) for the multidrug resistance 1 protein, suggesting low likelihood of brain uptake being affected by P\u2010glycoprotein. Cerebellum was used as a reference region in all imaging studies across all species due to the low levels of <jats:sup>18<\/jats:sup>F\u2010Mefway binding. Consistent binding of <jats:sup>18<\/jats:sup>F\u2010Mefway in cortical regions, hippocampus, and raphe was observed across all species. <jats:sup>18<\/jats:sup>F\u2010Mefway in the human brain regions correlated with the known postmortem distribution of 5\u2010HT<jats:sub>1A<\/jats:sub> 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. <jats:sup>18<\/jats:sup>F\u2010Mefway appears to be an effective 5\u2010HT<jats:sub>1A<\/jats:sub> receptor imaging agent in all models, including humans. <jats:sup>18<\/jats:sup>F\u2010Mefway therefore may be used to quantify 5\u2010HT<jats:sub>1A<\/jats:sub> receptor distribution in brain regions for the study of various CNS disorders. J. Comp. Neurol. 524:1457\u20131471, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23919","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T15:41:07Z","timestamp":1446046867000},"page":"1457-1471","source":"Crossref","is-referenced-by-count":17,"title":["Comparative assessment of <sup>18<\/sup>F\u2010Mefway as a serotonin 5\u2010HT<sub>1A<\/sub> receptor PET imaging agent across species: Rodents, nonhuman primates, and humans"],"prefix":"10.1002","volume":"524","author":[{"given":"Jogeshwar","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California Irvine California 92697\u20105000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha K.","family":"Bajwa","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California Irvine California 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