COMPARATIVE STUDY
JOURNAL ARTICLE

Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States

Chihiro Yokoyama, Aya Mawatari, Akihiro Kawasaki, Chiho Takeda, Kayo Onoe, Hisashi Doi, Adrian Newman-Tancredi, Luc Zimmer, Hirotaka Onoe
International Journal of Neuropsychopharmacology 2016, 19 (12)
27608810

BACKGROUND: In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18 F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their "active state," but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors.

METHODS: Positron emission tomography scans were conducted in a cohort of common marmosets (n=4) using the serotonin 1A receptor biased agonist radiotracer, 18 F-F13714, compared with a well-characterized 18 F-labeled antagonist radiotracer, 18 F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions.

RESULTS: 18 F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the 18 F-MPPF. Whereas 18 F-MPPF showed highest binding in hippocampus and amygdala, 18 F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18 F-F13714 were about one-third of those observed with 18 F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions.

CONCLUSIONS: These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18 F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist.

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