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

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 ± 25.9 GBq/μmol (1.5 ± 0.7 Ci/μmol). [ 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.