Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To evaluate the feasibility of [18F]MNI-659 PET, a striatal PDE10A imaging tracer, as a imaging biomarker in PD.
Background: PDE10 is highly and specifically expressed in brain in striatal neurons, primarily medium spiny neurons. This enzyme plays a critical role in modifying striatal dopaminergic function via regulation of cyclic nucleotides. [18F]MNI-659 PET is a well-validated, highly specific PET radioligand for PDE10A.
Methods: Eight PD subjects (2 de novo and 6 treated with dopaminergics) and 12 healthy controls (HC) participated. All subjects underwent clinical assessments and were imaged with [18F]MNI-659 for 90 minutes. Standard uptake values were determined for the basal ganglia nuclei. Binding potentials (BPnd) were estimated using SRTM (cerebellum as reference). MRI imaging was also acquired on all subjects and co-aligned with the PET images.
Results: PD participants (7M, 1F; mean age 65.7y [range 61.6-69.0]; mean duration of diagnosis 8.0y [range 1.5-12.7]) were compared with HC (mean age 51.1 [range 28.9-77.0]). Treated PD subjects all manifest dyskinesia and on-off phenomena. For PD, mean total UPDRS score was 42.3 (range 7-80) and motor subscale 25.9 (range 5-52). Strong [18F]MNI-659 uptake was seen in all basal ganglia nuclei. The mean striatal BPnd among PD subjects was significantly lower than for the full HC cohort (2.29 vs. 2.73). However, a previously unreported age-dependence was noted in HC basal ganglia PDE10A signal, i.e. reduced signal with aging. Following age-adjustment, [18F]MNI-659 signal remained significantly lower in caudate in PD vs. HC (-15.6%, S.D. 14.9, P<0.05), but was similar to HC in other nuclei. No significant correlations were noted between any basal ganglia nuclei BPnd and several measures of disease severity, treatment, or duration.
Conclusions: In this cohort of de novo and treated PD subjects, there is good brain penetration and binding of [18F]MNI-659 in basal ganglia nuclei. Age-adjusted PDE10A expression by [18F]MNI-659 PET is significantly reduced specifically in caudate nucleus when compared to HC.
To cite this abstract in AMA style:
D.S. Russell, D.L. Jennings, O. Barret, G.D. Tamagnan, D. Alagille, J.P. Seibyl, K.L. Marek. Striatal PDE10 expression in Parkinson’s disease (PD) and healthy controls using [18F]MNI-659 PET imaging [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/striatal-pde10-expression-in-parkinsons-disease-pd-and-healthy-controls-using-18fmni-659-pet-imaging/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/striatal-pde10-expression-in-parkinsons-disease-pd-and-healthy-controls-using-18fmni-659-pet-imaging/