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

Chloe Clark-Papasavas; Joel T. Dunn; Suki Greaves; Andrew Mogg; Rosemary Gomes; Stuart Brownings; Kathy Liu; Bonnita Nwosu; Paul Marsden; John Joemon; Marcel Cleij; Robert Kessler; Robert Howard; Suzanne Reeves

doi:10.1002/gps.4090

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

Chloe Clark-Papasavas, Joel T. Dunn, Suki Greaves, Andrew Mogg, Rosemary Gomes, Stuart Brownings, Kathy Liu, Bonnita Nwosu, Paul Marsden, John Joemon, Marcel Cleij, Robert Kessler, Robert Howard, Suzanne Reeves^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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 (BP_ND) 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 BP_ND 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.

Original language	English
Pages (from-to)	1001-1009
Number of pages	9
Journal	International Journal of Geriatric Psychiatry
Volume	29
Issue number	10
DOIs	https://doi.org/10.1002/gps.4090
Publication status	Published - Oct 2014

Keywords

Alzheimer's disease
Amisulpride
Antipsychotic
D2/3 occupancy
Psychosis
[F]fallypride

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10.1002/gps.4090

Cite this

Clark-Papasavas, C., Dunn, J. T., Greaves, S., Mogg, A., Gomes, R., Brownings, S., Liu, K., Nwosu, B., Marsden, P., Joemon, J., Cleij, M., Kessler, R., Howard, R., & Reeves, S. (2014). Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [¹⁸F] fallypride positron emission tomography. International Journal of Geriatric Psychiatry, 29(10), 1001-1009. https://doi.org/10.1002/gps.4090

@article{e59da71332654b729090f47cec03cae1,

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.",

keywords = "Alzheimer's disease, Amisulpride, Antipsychotic, D2/3 occupancy, Psychosis, [F]fallypride",

author = "Chloe Clark-Papasavas and Dunn, {Joel T.} and Suki Greaves and Andrew Mogg and Rosemary Gomes and Stuart Brownings and Kathy Liu and Bonnita Nwosu and Paul Marsden and John Joemon and Marcel Cleij and Robert Kessler and Robert Howard and Suzanne Reeves",

year = "2014",

month = oct,

doi = "10.1002/gps.4090",

language = "English",

volume = "29",

pages = "1001--1009",

journal = "International Journal of Geriatric Psychiatry",

issn = "0885-6230",

publisher = "John Wiley and sons",

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Clark-Papasavas, C , Dunn, JT, Greaves, S, Mogg, A, Gomes, R , Brownings, S, Liu, K, Nwosu, B , Marsden, P, Joemon, J, Cleij, M, Kessler, R, Howard, R & Reeves, S 2014, 'Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [¹⁸F] fallypride positron emission tomography', International Journal of Geriatric Psychiatry, vol. 29, no. 10, pp. 1001-1009. https://doi.org/10.1002/gps.4090

Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [¹⁸F] fallypride positron emission tomography. / Clark-Papasavas, Chloe ; Dunn, Joel T.; Greaves, Suki et al.
In: International Journal of Geriatric Psychiatry, Vol. 29, No. 10, 10.2014, p. 1001-1009.

Research output: Contribution to journal › Article › peer-review

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

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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 -