title: Determination of dopamine D₂ receptor occupancy by lurasidone using positron emission tomography in healthy male subjects.
abstract: BACKGROUND
  A positron emission tomography (PET) study of dopamine D₂ receptor occupancy was conducted to support a rational dose selection for clinical efficacy studies with lurasidone, an atypical antipsychotic that was approved for the treatment of schizophrenia by the FDA in late 2010.
  
  
  OBJECTIVE
  To determine the dopamine D₂ receptor occupancy of lurasidone in the ventral striatum, putamen and caudate nucleus, and to characterize the relationship between lurasidone serum concentration and D₂ receptor occupancy.
  
  
  METHODS
  A single oral dose of lurasidone (10, 20, 40, 60, or 80 mg) was administered sequentially to healthy male subjects (n = 4 in each cohort). Two PET scans were performed. For each scan, 20 mCi of [¹¹C]raclopride was administered intravenously as a bolus injection, followed immediately by 90 min of PET scan acquisitions.
  
  
  RESULTS
  The D₂ receptor occupancy levels were 41-43% for 10 mg, 51-55% for 20 mg, 63-67% for 40 mg, 77-84% for 60 mg, and 73-79% for 80 mg of lurasidone. The relationship between D₂ receptor occupancy and the mean serum lurasidone concentration during the PET scan (C PET) was similar for the putamen, caudate nucleus, and ventral striatum regions. Mean D₂ receptor occupancy levels correlated well with average peak serum concentration of lurasidone.
  
  
  CONCLUSIONS
  In healthy volunteers, single doses of lurasidone 40-80 mg resulted in D₂ receptor occupancy levels of >60%, a level of receptor occupancy previously associated with clinical response for atypical antipsychotics.
authors: Department of Radiology, Johns Hopkins Medical Institutions (JHMI), 601 North Caroline Street, Room JHOC 3245, Baltimore, MD 21287-0807, USA. dfwong@jhmi.edu
authors: Dean F
authors: DF
authors: Wong
authors: Hiroto
authors: H
authors: Kuwabara
authors: James Robert
authors: JR
authors: Brašić
authors: Thomas
authors: T
authors: Stock
authors: Atul
authors: A
authors: Maini
authors: Emily G
authors: EG
authors: Gean
authors: Antony
authors: A
authors: Loebel
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D064368:Healthy Volunteers; D006801:Humans; D054833:Isoindoles / Q000494:pharmacology*; D000069056:Lurasidone Hydrochloride; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D054833:Isoindoles; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride
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