title: Fluorine-18-Labeled Antagonist for PET Imaging of Kappa Opioid Receptors.
abstract: Kappa opioid receptor (KOR) antagonists are potential drug candidates for diseases such as treatment-refractory depression, anxiety, and addictive disorders. PET imaging radiotracers for KOR can be used in occupancy study to facilitate drug development, and to investigate the roles of KOR in health and diseases. We have previously developed two11C-labeled antagonist radiotracers with high affinity and selectivity toward KOR. What is limiting their wide applications is the short half-life of11C. Herein, we report the synthesis of a first18F-labeled KOR antagonist radiotracer and the initial PET imaging study in a nonhuman primate.
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Cai
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Songye
authors.initials: S
authors.lastname: Li
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Pracitto
authors.affiliation: Eli Lilly and Company , Indianapolis, Indiana 46285, United States.
authors.forename: Antonio
authors.initials: A
authors.lastname: Navarro
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Anupama
authors.initials: A
authors.lastname: Shirali
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: PET Center, Department of Radiology and Biomedical Imaging, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D005461:Fluorine / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D009292:Narcotic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D066244:Proton Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D001549:Benzamides; C000599322:LY2459989; D009292:Narcotic Antagonists; D011725:Pyridines; D017473:Receptors, Opioid, kappa; D005461:Fluorine
keywords: Kappa opioid receptor; PET; fluorination; iodonium ylide; microfluidic; nonhuman primate