In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: Studies in non-human primates and transgenic mice (original) (raw)

Examination of dopamine-D3 (D3) receptors with positron emission tomography (PET) have been hampered in the past by the lack of a PET ligand with sufficient selectivity for D3 over dopamine-D2 (D2) receptors. The two types co-localize in the brain, with D2 density significantly higher than D3, hence nonselective PET ligands inform on D2, rather than D3 status. [ 11 C]-(1)-PHNO is a novel PET ligand with a preferential affinity for D3 over D2. We used the selective D3 antagonist, SB-277011 to dissect regional fractions of the [ 11 C]-(1)-PHNO signal attributable to D3 and D2 in primate brain. The results were compared with quantitative autoradiography with 3 H-(1)-PHNO in wild-type, D2-knockout , and D3-knockout mice examined at baseline and following administration of SB-277011. Both sets of results converged to indicate a predominant D3-related component to (1)-PHNO binding in extra-striatal regions, with binding in the midbrain being entirely attributable to D3. The midbrain is thus an excellent target region to examine D3 receptor occupancy with [ 11 C]-(1)-PHNO PET in vivo.