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

• Published in: Neurology Vol. 86; no. 3; p. 224
• Main Authors: Payer, Doris E, Guttman, Mark, Kish, Stephen J, Tong, Junchao, Adams, John R, Rusjan, Pablo, Houle, Sylvain, Furukawa, Yoshiaki, Wilson, Alan A, Boileau, Isabelle
• Format: Journal Article
• Language: English
• Published: United States 19.01.2016
• Subjects: 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
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000002285

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