Investigation of an F-18 oxytocin receptor selective ligand via PET imaging

• Type of Material: Article
• Authors: Aaron Smith, Emory University; Sara M. Freeman, Yerkes National Primate Research Center; Ronald Voll, Emory University; Larry J Young, Emory University; Mark Goodman, Emory University
• Language: English
• Date: 2013-10-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bmcl.2013.07.045
• Title of Journal or Parent Work: Bioorganic and Medicinal Chemistry Letters
• ISSN: 0960-894X
• Volume: 23
• Issue: 19
• Start Page: 5415
• End Page: 5420
• Grant/Funding Information: We also acknowledge NIH MH064692 (L.J.Y.) and the National Center for Research Resources P51RR165 (currently P51OD11132) to YNPRC.; This research was funded by the National Institute of Mental Health through grant 5 R21 MH090776.
• Keywords: Fluorine-18; Oxytocin receptor; Choroid plexus; PET imaging; Receptor imaging; Alpha-1 adrenergic receptor; Cerebral ventricles; Oxytocin; Adrenergic receptor
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience

Abstract

The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin- 2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vivo via PET imaging using rat and cynomolgus monkey models. PET imaging studies in female Sprague–Dawley rats suggested [F-18]1 reached the brain and accumulated in various regions of the brain, but washed out too rapidly for adequate quantification and localization. In vivo PET imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain penetration while specific uptake of radioactivity significantly accumulated within the vasculature of the cerebral ventricles in areas representative of the choroid plexus.