Comparative assessment of (18) F-Mefway as a serotonin 5-HT1A receptor PET imaging agent across species: Rodents, nonhuman primates, and humans

J Comp Neurol. 2016 May 1;524(7):1457-71. doi: 10.1002/cne.23919. Epub 2015 Nov 18.


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.

Keywords: P-glycoprotein; hippocampus; raphe nucleus; receptor selectivity; translational research.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Mapping
  • Dose-Response Relationship, Drug
  • Female
  • Fourier Analysis
  • Humans
  • Image Processing, Computer-Assisted
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Piperazines / pharmacokinetics*
  • Positron-Emission Tomography
  • Prazosin / pharmacology
  • Protein Binding / drug effects
  • Pyridines / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin Receptor Agonists / pharmacology


  • Adrenergic alpha-1 Receptor Antagonists
  • Piperazines
  • Pyridines
  • Radiopharmaceuticals
  • Serotonin Receptor Agonists
  • mefway
  • Receptor, Serotonin, 5-HT1A
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Prazosin