Objective: To longitudinally assess presynaptic terminal loss in vivo over a 2-year period in people with early Parkinson’s disease (PD).

Background: Imaging tools that allow quantification of PD progression could facilitate the development of disease-modifying therapeutics. Cross-sectional studies have shown presynaptic terminal damage in PD patients, but longitudinal data are limited.

Method: 27 patients with early PD (62.7 ± 9.8 years, 8F/19M) and 18 age- and sex-matched healthy controls (HC, 61.3 ± 8.6 years, 5F/13M) underwent PET with ¹¹C‑UCB‑J, a ligand for the brain-wide presynaptic terminal marker SV2A, and with ¹⁸F‑FE‑PE2I, a highly selective dopamine transporter ligand, in combination with a comprehensive clinical assessment of motor and non-motor manifestations at baseline (BL) and after 26.5 ± 2.1 months (Y2). Volumes of interest were delineated based on individual 3D T1 MRI. For both tracers, SUVR‑1 images were calculated. Within-group 2-year differences in clinical and imaging outcomes were assessed. Additionally, 2-year differences were compared between PD and HC. In the PD group, correlations between imaging and clinical scores were calculated.

Results: PD patients showed significant 2-year worsening of MDS-UPDRS II and MDS-UPDRS III (in practically defined OFF state) scores, but not of non-motor scores. Motor and non-motor scores did not change significantly in HC. Volumetric analysis did not show significant atrophy in PD patients compared with HD at BL or Y2. Compared with HC, ¹¹C‑UCB‑J binding was decreased in the substantia nigra in PD at BL and at Y2, but ¹¹C‑UCB‑J PET did not show any region with significant 2-year change in PD or HC. ¹⁸F‑FE‑PE2I PET showed significant decline in the PD group between BL and Y2, with an annualized change of ‑7.8 ± 7.9% in caudate, ‑10.7 ± 7.0% in putamen (both p < 0.001) and ‑4.5 ± 13.2% in substantia nigra (p = 0.02). In HC, no difference in ¹⁸F‑FE‑PE2I binding between BL and Y2 was found. The 2-year decline in ¹⁸F‑FE‑PE2I binding in PD patients did not correlate with longitudinal changes in MDS-UPDRS II or III scores.

Conclusion: ¹¹C‑UCB‑J binding characteristics did not show significant changes over 2 years in early PD patients. By contrast, ¹⁸F‑FE‑PE2I PET showed robust 2-year decline in early PD, but without correlation with motor progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-combined-11c-ucb-j-and-18f-fe-pe2i-pet-imaging-of-presynaptic-terminal-loss-in-early-parkinsons-disease/