Fluorine-18-Labeled Antagonist for PET Imaging of Kappa Opioid Receptors

ACS Chem Neurosci. 2017 Jan 18;8(1):12-16. doi: 10.1021/acschemneuro.6b00268. Epub 2016 Oct 20.

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 two 11C-labeled antagonist radiotracers with high affinity and selectivity toward KOR. What is limiting their wide applications is the short half-life of 11C. Herein, we report the synthesis of a first 18F-labeled KOR antagonist radiotracer and the initial PET imaging study in a nonhuman primate.

Keywords: Kappa opioid receptor; PET; fluorination; iodonium ylide; microfluidic; nonhuman primate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacokinetics
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Fluorine / pharmacokinetics*
  • Macaca mulatta
  • Narcotic Antagonists* / chemical synthesis
  • Narcotic Antagonists* / chemistry
  • Narcotic Antagonists* / pharmacokinetics
  • Positron-Emission Tomography*
  • Proton Magnetic Resonance Spectroscopy
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, kappa / metabolism*

Substances

  • Benzamides
  • LY2459989
  • Narcotic Antagonists
  • Pyridines
  • Receptors, Opioid, kappa
  • Fluorine