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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

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We investigated feasibility of positron emission tomography (PET) with [11C]SA4503 for evaluating the sigmai receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D2-like receptor (D2R) as well as to be a representative non-selective antagonist for sigmai receptor (σ1R), was selected as a model drug. Three healthy male subjects underwent 60-min [11C]raclopride-PET and 90-min [11C]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 [11C]raclopride and [11C]SA4503 was quantitatively evaluated and the σ1R 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 σ1R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the σlR receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [11C]SA4503-PET can be used for evaluating the σlR occupancy rates by neuroleptics or other drugs.

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Correspondence to Kiichi Ishiwata.

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Ishiwata, K., Oda, K., Sakata, M. et al. 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. Ann Nucl Med 20, 569–573 (2006).

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