D3 dopamine receptor-preferring [11C]PHNO PET imaging in Parkinson patients with dyskinesia

Doris E Payer; Mark Guttman; Stephen J Kish; Junchao Tong; John R Adams; Pablo Rusjan; Sylvain Houle; Yoshiaki Furukawa; Alan A Wilson; Isabelle Boileau

doi:10.1212/WNL.0000000000002285

D3 dopamine receptor-preferring [11C]PHNO PET imaging in Parkinson patients with dyskinesia

Neurology. 2016 Jan 19;86(3):224-30. doi: 10.1212/WNL.0000000000002285. Epub 2015 Dec 30.

Authors

Affiliations

¹ From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
² From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada. isabelle.boileau@camh.ca.

Abstract

Objective: To investigate whether levodopa-induced dyskinesias (LID) are associated with D3 overexpression in levodopa-treated humans with Parkinson disease (PD).

Methods: In this case-control study, we used PET with the D3-preferring radioligand [(11)C]-(+)-PHNO to estimate D2/3 receptor binding in patients with levodopa-treated PD with LID (n = 12) and without LID (n = 12), and healthy control subjects matched for age, sex, education, and mental status (n = 18).

Results: Compared to nondyskinetic patients, those with LID showed heightened [(11)C]-(+)-PHNO binding in the D3-rich globus pallidus. Both PD groups also showed higher binding than controls in the sensorimotor division of the striatum. In contrast, D2/3 binding in the ventral striatum was lower in patients with LID than without, possibly reflecting higher dopamine levels.

Conclusions: Dopaminergic abnormalities contributing to LID may include elevated D2/3 binding in globus pallidus, perhaps reflecting D3 receptor upregulation. The findings support therapeutic strategies that target and diminish activity at D3 to prevent LID.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carbon Radioisotopes
Case-Control Studies
Dopamine Agents / adverse effects*
Dyskinesia, Drug-Induced / diagnostic imaging*
Dyskinesia, Drug-Induced / etiology
Female
Globus Pallidus / diagnostic imaging*
Humans
Levodopa / adverse effects*
Male
Middle Aged
Neostriatum / diagnostic imaging
Parkinson Disease / diagnostic imaging*
Parkinson Disease / drug therapy
Positron-Emission Tomography / methods*
Receptors, Dopamine D2 / agonists
Receptors, Dopamine D2 / metabolism
Receptors, Dopamine D3 / agonists
Receptors, Dopamine D3 / metabolism*
Up-Regulation
Ventral Striatum / diagnostic imaging

Substances

Carbon Radioisotopes
Dopamine Agents
Receptors, Dopamine D2
Receptors, Dopamine D3
Levodopa