Design, synthesis and preliminary evaluation of (18)F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2532-5. doi: 10.1016/j.bmcl.2015.04.055. Epub 2015 Apr 25.

Abstract

In the present work, we report the synthesis of new aryliodonium salts used as precursors of single-stage nucleophilic (18)F radiofluorination. The corresponding unlabelled fluorinated derivatives showed to be CB2 cannabinoid receptor specific ligands, with Ki values in the low nanomolar range and high CB2/CB1 selectivity. The radiolabelled compound [(18)F]CB91, was successfully formulated for in vivo administration, and its preliminary biodistribution was assessed with microPET/CT. This tracer presented a reasonable in vivo stability and a preferential extraction in the tissues that constitutionally express CB2 cannabinoid receptor. The results obtained indicate [(18)F]CB91 as a possible candidate marker of CB2 cannabinoid receptor distribution. This study would open the way to further validation of this tracer for assessing pathologies for which the expression of this receptor is modified.

Keywords: CB2 receptor; Cannabinoid; Iodonium derivatives; Microfluidic system; Radiofluorination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacokinetics
  • Animals
  • Contrast Media / chemical synthesis*
  • Contrast Media / chemistry
  • Drug Design*
  • Fluorine Radioisotopes / chemistry
  • Isomerism
  • Male
  • Mice
  • Naphthyridines / chemical synthesis*
  • Naphthyridines / chemistry
  • Naphthyridines / pharmacokinetics
  • Positron-Emission Tomography
  • Quinolones / chemistry
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / chemistry
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Tissue Distribution

Substances

  • Amides
  • CB91 compound
  • Contrast Media
  • Fluorine Radioisotopes
  • Naphthyridines
  • Quinolones
  • Radiopharmaceuticals
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2