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

Abstract

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. 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. 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). The protocol is feasible for use in AD and represents the first step towards establishing dose-occupancy relationships across older clinical populations.