2. Academic Validation
  3. A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging

A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging

  • Molecules. 2020 Feb 25;25(5):1018. doi: 10.3390/molecules25051018.
Ping Bai 1 2 3,  Sha Bai 2,  Michael S Placzek 2,  Xiaoxia Lu 1,  Stephanie A Fiedler 2,  Brenda Ntaganda 2,  Hsiao-Ying Wey 2,  Changning Wang 2
Affiliations

Affiliations

  • 1 Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
  • 2 Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
  • 3 University of Chinese Academy of Sciences, Beijing 100049, China.
PMID: 32106419 DOI: 10.3390/molecules25051018
Abstract

The orexin receptor (OX) is critically involved in motivation and sleep-wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([11C]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC50 = 0.253 μM and 1.406 μM for OX1R and OX2R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [11C]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [11C]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.

Keywords

PET; imaging; orexin receptors; radiotracer.

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