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

Compound 1 is a potent and selective antagonist of the dopamine D3 receptor. With the aim of developing a carbon-11 labeled ligand for the dopamine D3 receptor, 1 was selected as a potential PET probe. [11C]1 was obtained by palladium catalyzed cross coupling using [11C]cyanide and 4 with a specific activity of 55.5 ± 25.9 GBq/μmol (1.5 ± 0.7 Ci/μmol). [11C]1 was tested in porcine and non-human primate models to assess its potential as a radioligand for PET imaging of the dopamine D3 receptor. We conclude that in both species and despite appropriate in vitro properties, [11C]1 does not show any specific signal for the dopamine D3 receptor.

Graphical abstractRadiosynthesis and in vivo testing for a potential Dopamine D3 PET ligand are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide