Synthesis and in vitro autoradiographic evaluation of a novel high-affinity radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6209-12. doi: 10.1016/j.bmcl.2009.08.092. Epub 2009 Sep 3.

Abstract

There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB1) receptors in neuropsychiatric disorders with single photon emission computed tomography (SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB1 receptor ligand ([125I]8, [125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, [125I]SD7015). By autoradiography in vitro, [125I]8 showed selective binding to CB1 receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate.

Publication types

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

MeSH terms

  • Brain / diagnostic imaging*
  • Humans
  • Iodine Radioisotopes
  • Ligands*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Tomography, Emission-Computed, Single-Photon

Substances

  • 1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate
  • 4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
  • Iodine Radioisotopes
  • Ligands
  • Piperidines
  • Pyrazoles
  • Radiopharmaceuticals
  • Receptor, Cannabinoid, CB1