A feasibility study of [ super(11)C]SA4503-PET for evaluating sigma sub(1) receptor occupancy by neuroleptics: The binding of haloperidol to sigma sub(1) and dopamine D sub(2)-like receptors

We investigated feasibility of positron emission tomography (PET) with [ super(11)C]SA4503 for evaluating the sigmai receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D sub(2)-like receptor (D2R) as well as to be a representative non-selective antagonist for sigmai receptor (s1R), was selected as a model drug. Three healthy male subjects underwent 60-min [ super(11)C]raclopride-PET and 90-min [ super(11)C]SA4503-PET scans successively at a 120-min interval twice in a day for baseline measurement and on another day for haloperidol-loading measurement 16 hours after peroral administration of 3 mg of haloperidol. Binding potential (BP) of [ super(11)C]raclopride and [ super(11)C]SA4503 was quantitatively evaluated and the s1R and D2R occupancy rates were determined. D2R occupancy rates by haloperidol were 64% and 62% in the caudate and putamen, respectively, 16 h after the administration, while s1R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the slR receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [ super(11)C]SA4503-PET can be used for evaluating the slR occupancy rates by neuroleptics or other drugs.