title: Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys.
abstract: The neuropeptide oxytocin is part of a neuroendocrine system that has physiological effects ranging from ensuring uterine myometrial contractions at parturition and post-partum mammary gland milk ejection to the modulation of neural control of social relationships. This initial study was performed to investigate the potential use of positron emission tomography (PET) for localizing oxytocin receptors in two New World primates. Three biomarkers for PET (1-3) that are known to have high affinity and selectivity for the human oxytocin receptor were investigated in the common marmoset (Callithrix jacchus) via PET imaging. Brain penetration, and uptake in the salivary gland area were both observed with biomarkers 2 and 3. No brain penetration was observed with 1, but uptake was observed more specifically in several peripheral endocrine glands compared to 2 or 3. Biomarker 2, which displayed the best brain penetration of the three biomarkers in the marmoset, was then investigated in the monogamous coppery titi monkey (Callicebus cupreus) in a brain scan and a limited full body scan. No significant brain penetration of 2 was observed in the titi monkey, but significant uptake was observed in various locations throughout the periphery. Metabolism of 2 was suspected to have been significant based upon HPLC analysis of blood draws, but parent compound was still present near the end of the scan. Follow-up investigations will focus on next generation biomarkers bearing improved binding characteristics and brain penetrability as well as investigating tissue in regions where biomarker uptake was observed.
authors.affiliation: Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Smith
authors.affiliation: Department of Psychology, University of California, Davis, CA 95616, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Freeman
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Abbott
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Ahlers
authors.affiliation: Center for Molecular and Genomic Imaging, University of California, Davis, CA 95616, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kukis
authors.affiliation: Department of Psychology, University of California, Davis, CA 95616, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Bales
authors.affiliation: Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
authors.affiliation: Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. Electronic address: lyoun03@emory.edu.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Young
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D051078:Platyrrhini; D049268:Positron-Emission Tomography; D018045:Receptors, Oxytocin / Q000032:analysis* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D015415:Biomarkers; D008024:Ligands; D018045:Receptors, Oxytocin; D054852:Small Molecule Libraries
keywords: Marmoset; Oxytocin; Oxytocin receptor; PET imaging; Titi monkey; Vasopressin; Vasopressin receptor