Longitudinal Positron Emission Tomography Imaging of Presynaptic Terminals in Early Parkinson's Disease

Abstract Background Imaging tools that allow quantification of Parkinson's disease (PD) progression could facilitate the development of disease‐modifying therapies. Cross‐sectional studies have shown presynaptic terminal damage in PD patients, but longitudinal data are limited. Objectives The aim of this study was to longitudinally assess loss of presynaptic terminals in general and dopaminergic presynaptic terminals in particular as measures of disease progression in early PD. Methods A total of 27 patients with early PD and 18 age‐ and sex‐matched healthy controls underwent positron emission tomography (PET) with 11 C‐UCB‐J, a ligand for the brain‐wide presynaptic terminal marker SV2A, and with 18 F‐FE‐PE2I, a highly selective dopamine transporter ligand, in combination with a comprehensive motor and non‐motor clinical assessment at baseline (BL) and after 26.5 ± 2.1 months (Y2). SUVR‐1 images were calculated and volumes of interest were delineated based on individual 3D T1 magnetic resonance imaging (MRI). Results PD patients showed significant 2‐year worsening of Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS‐UPDRS‐III) ( off medication) scores, but not of non‐motor scores. Motor and non‐motor scores in controls did not change significantly over 2 years. 18 F‐FE‐PE2I binding in caudate and putamen showed significant 2‐year decline in the PD group and remained unchanged in controls. Longitudinal decline of striatal 18 F‐FE‐PE2I binding in PD did not correlate with longitudinal changes in MDS‐UPDRS‐III scores. 11 C‐UCB‐J PET did not show any region with significant 2‐year change in PD or controls. Conclusions 18 F‐FE‐PE2I PET showed robust 2‐year decline in early PD, but 11 C‐UCB‐J PET did not. Longitudinal changes in 18 F‐FE‐PE2I binding did not correlate with clinical motor progression. © 2022 International Parkinson and Movement Disorder Society.