Fluorine-18 isotope labeling for positron emission tomography imaging. Direct evidence for DBPR211 as a peripherally restricted CB1 inverse agonist

Bioorg Med Chem. 2019 Jan 1;27(1):216-223. doi: 10.1016/j.bmc.2018.11.043. Epub 2018 Nov 29.

Abstract

The [18F] isotope-labelled CB1 inverse agonist 3 was elaborated and synthesized for positron emission tomography scanning studies. After immediate purification and calibration with its unlabeled counterpart, compound 3 was intravenously injected in mice and revealed that its distribution percentage in brain over 90-min scans among five region of interests, including brain, liver, heart, thigh muscle and kidney was lower than 1%, thus providing direct evidence to justify itself as a peripherally restricted CB1 antagonist.

Keywords: Blood-brain barrier; Cannabinoid-1 antagonist; Peripherally restricted CB1 inverse agonist; Positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists / chemical synthesis
  • Cannabinoid Receptor Agonists / chemistry
  • Cannabinoid Receptor Agonists / pharmacokinetics
  • Cannabinoid Receptor Agonists / pharmacology*
  • Drug Inverse Agonism
  • Fluorine Radioisotopes
  • Isotope Labeling
  • Male
  • Mice, Inbred C57BL
  • Positron-Emission Tomography / methods
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology*
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology*
  • Thiophenes / chemistry
  • Thiophenes / pharmacokinetics
  • Thiophenes / pharmacology*
  • Tissue Distribution

Substances

  • Cannabinoid Receptor Agonists
  • Fluorine Radioisotopes
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Sulfonamides
  • Thiophenes
  • Fluorine-18