title: Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [18F]fallypride positron emission tomography.
abstract: OBJECTIVE
  Dopamine D2/3 receptor positron emission tomography tracers have guided antipsychotic prescribing in young people with schizophrenia by establishing a 'therapeutic window' of striatal D2/3 receptor occupancy. Older people, particularly those with dementia, are highly susceptible to motor side effects and may benefit from the appropriate application of imaging techniques. The study aimed to adapt [18F]fallypride imaging for use in occupancy studies in Alzheimer's disease (AD) and to investigate whether data acquisition could be made more tolerable by piloting the protocol in a small sample.
  
  
  METHODS
  Six participants with AD (three men; 85.0 ± 5.6 years old; MMSE = 16.0 ± 2.4) were recruited prior to commencing amisulpride for the treatment of psychosis and associated agitation. [18F]fallypride binding potential (BPND ) was determined using an interrupted scanning protocol at baseline (n = 6) and after 27.0 ± 6.1 days of amisulpride (25-50 mg) treatment (n = 4). D2/3 occupancy was calculated by percentage reduction in BPND between scanning sessions. Image data were re-analysed after reducing individual sampling times to 20 min.
  
  
  RESULTS
  The protocol was tolerated well, apart from the final (40 min) session of the post-treatment scan in one participant. Higher occupancies were achieved in the striatum (caudate 47-70%, putamen 31-58%) and thalamus (54-76%) than in the inferior temporal gyrus (27-43%). There was high agreement between occupancy values derived using longer and shorter sampling times (mean absolute difference 6.1% in the inferior temporal gyrus; <2% all other regions).
  
  
  CONCLUSIONS
  The protocol is feasible for use in AD and represents the first step towards establishing dose-occupancy relationships across older clinical populations.
authors.affiliation: Department of Old Age Psychiatry, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Clark-Papasavas
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dunn
authors.forename: Suki
authors.initials: S
authors.lastname: Greaves
authors.forename: Andrew
authors.initials: A
authors.lastname: Mogg
authors.forename: Rosemary
authors.initials: R
authors.lastname: Gomes
authors.forename: Stuart
authors.initials: S
authors.lastname: Brownings
authors.forename: Kathy
authors.initials: K
authors.lastname: Liu
authors.forename: Bonnita
authors.initials: B
authors.lastname: Nwosu
authors.forename: Paul
authors.initials: P
authors.lastname: Marsden
authors.forename: John
authors.initials: J
authors.lastname: Joemon
authors.forename: Marcel
authors.initials: M
authors.lastname: Cleij
authors.forename: Robert
authors.initials: R
authors.lastname: Kessler
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
authors.forename: Suzanne
authors.initials: S
authors.lastname: Reeves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism*; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001549:Benzamides / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000077582:Amisulpride; C574003:fallypride
keywords: Alzheimer's disease; D2/3 occupancy; [18F]fallypride; amisulpride; antipsychotic; psychosis