Dopamine D3 receptor antagonists: the quest for a potentially selective PET ligand. Part 3: Radiosynthesis and in vivo studies

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5056-9. doi: 10.1016/j.bmcl.2009.07.055. Epub 2009 Jul 25.

Abstract

Compound 1 is a potent and selective antagonist of the dopamine D(3) receptor. With the aim of developing a carbon-11 labeled ligand for the dopamine D(3) receptor, 1 was selected as a potential PET probe. [(11)C]1 was obtained by palladium catalyzed cross coupling using [(11)C]cyanide and 4 with a specific activity of 55.5+/-25.9GBq/micromol (1.5+/-0.7Ci/micromol). [(11)C]1 was tested in porcine and non-human primate models to assess its potential as a radioligand for PET imaging of the dopamine D(3) receptor. We conclude that in both species and despite appropriate in vitro properties, [(11)C]1 does not show any specific signal for the dopamine D(3) receptor.

MeSH terms

  • Animals
  • Carbon Radioisotopes / chemistry
  • Haplorhini
  • Humans
  • Imidazolidines / chemical synthesis*
  • Imidazolidines / chemistry
  • Ligands
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Rats
  • Receptors, Dopamine D3 / antagonists & inhibitors*
  • Receptors, Dopamine D3 / metabolism
  • Swine

Substances

  • Carbon Radioisotopes
  • Imidazolidines
  • Ligands
  • Piperidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D3