[ 18F]fallypride characterization of striatal and extrastriatal D 2/3 receptors in Parkinson's disease

• Published in: NeuroImage clinical Vol. 18; pp. 433 - 442
• Main Authors: Stark, Adam J, Smith, Christopher T, Petersen, Kalen J, Trujillo, Paula, van Wouwe, Nelleke C, Donahue, Manus J, Kessler, Robert M, Deutch, Ariel Y, Zald, David H, Claassen, Daniel O
• Format: Journal Article
• Language: English
• Published: Netherlands 2018
• Subjects: Aged; Aged, 80 and over; Benzamides - pharmacokinetics; Brain Mapping; Corpus Striatum - diagnostic imaging; Corpus Striatum - drug effects; Dopamine D2 Receptor Antagonists - pharmacokinetics; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Humans; Magnetic Resonance Imaging; Male; Parkinson Disease - diagnostic imaging; Positron-Emission Tomography; Radiology; Receptors, Dopamine D2 - metabolism; Positron emission tomography (PET); Binding potential (nondisplaceable); Parkinson's disease; Dopamine; MoCA; Montreal Cognitive Assessment; Movement Disorders Society-United Parkinson's disease Rating Scale; Levodopa Daily Dose; Region of Interest; ROI; BP ND; Healthy controls; PD; Neurodegeneration; Fallypride; CES-D; LEDD; HC; Positron emission tomography; Center for Epidemiologic Studies Depression Scale; MDS-UPDRS; PET; PET, Positron emission tomography; LEDD, Levodopa Daily Dose; MoCA, Montreal Cognitive Assessment; BPND, Binding potential (nondisplaceable); CES-D, Center for Epidemiologic Studies Depression Scale; PD, Parkinson's disease; MDS-UPDRS, Movement Disorders Society-United Parkinson's disease Rating Scale; ROI, Region of Interest; HC, Healthy controls
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2018.02.010

AbstractParkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.