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Comparative assessment of 18 F‐Mefway as a serotonin 5‐HT 1A receptor PET imaging agent across species: Rodents, nonhuman primates, and humans
Author(s) -
Mukherjee Jogeshwar,
Bajwa Alisha K.,
Wooten Dustin W.,
Hillmer Ansel T.,
Pan MinLiang,
Pandey Suresh K.,
Saigal Neil,
Christian Bradley T.
Publication year - 2015
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23919
Subject(s) - biology , receptor , raphe nuclei , 5 ht receptor , human brain , serotonin , radioligand , neuroscience , hippocampus , cerebellum , medicine , serotonergic , biochemistry
ABSTRACT We have developed 18 F‐ trans ‐Mefway ( 18 F‐Mefway) for positron emission tomography (PET) imaging studies of serotonin 5‐HT 1A receptors which are implicated in various brain functions. Translation of imaging the 5‐HT 1A 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‐HT 1A 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‐HT 1A 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‐HT 1A receptor imaging agent in all models, including humans. 18 F‐Mefway therefore may be used to quantify 5‐HT 1A receptor distribution in brain regions for the study of various CNS disorders. J. Comp. Neurol. 524:1457–1471, 2016. © 2015 Wiley Periodicals, Inc.