title: A feasibility study of [11C]SA4503-PET for evaluating sigmal receptor occupancy by neuroleptics: the binding of haloperidol to sigma1 and dopamine D2-like receptors.
abstract: We investigated feasibility of positron emission tomography (PET) with [11C]SA4503 for evaluating the sigma1 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 sigma1 receptor (sigma1R), 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 sigma1R 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 sigma1R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the sigma1R 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 sigma1R occupancy rates by neuroleptics or other drugs.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan. ishiwata@pet.tmig.or.jp
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Kenji
authors.initials: K
authors.lastname: Oda
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Sakata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Oda
authors.forename: Toru
authors.initials: T
authors.lastname: Sasaki
authors.forename: Mika
authors.initials: M
authors.lastname: Naganawa
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Chihara
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005240:Feasibility Studies; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018697:Nootropic Agents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; C101789:SA 4503; D006220:Haloperidol