A feasibility study of [11C]SA4503-PET for evaluating sigma1 receptor occupancy by neuroleptics:: the binding of haloperidol to sigma1 and dopamine D2-like receptors

We investigated feasibility of positron emission tomography (PET) with [C-11]SA4503 for evaluating the sigma(1) receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D-2-like receptor (D2R) as well as to be a representative non-selective antagonist for sigma I receptor (at R), was selected as a model drug. Three healthy male subjects underwent 60-min [C-11]raclopride-PET and 90-min [C-11]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 halopefidol. Binding potential (BP) of [C-11]raclopfide and [C-11]SA4503 was quantitatively evaluated and the sigma 1R 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 at R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the at R receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [C-11]SA4503-PET can be used for evaluating the sigma lR occupancy rates by neuroleptics or other drugs.