Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [¹⁸F] fallypride positron emission tomography

TY - JOUR

T1 - Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [18F] fallypride positron emission tomography

AU - Clark-Papasavas, Chloe

AU - Dunn, Joel T.

AU - Greaves, Suki

AU - Mogg, Andrew

AU - Gomes, Rosemary

AU - Brownings, Stuart

AU - Liu, Kathy

AU - Nwosu, Bonnita

AU - Marsden, Paul

AU - Joemon, John

AU - Cleij, Marcel

AU - Kessler, Robert

AU - Howard, Robert

AU - Reeves, Suzanne

PY - 2014/10

Y1 - 2014/10

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amisulpride

KW - Antipsychotic

KW - D2/3 occupancy

KW - Psychosis

KW - [F]fallypride

UR - https://www.scopus.com/pages/publications/84908674641

U2 - 10.1002/gps.4090

DO - 10.1002/gps.4090

M3 - Article

AN - SCOPUS:84908674641

SN - 0885-6230

VL - 29

SP - 1001

EP - 1009

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 10

ER -