Objective: This study aimed to determine the potential of a novel α-syn tracer, ¹⁸F-FD4 PET, to track regional α-synuclein deposition in PD and explore its correlation with disease severity.

Background: Parkinson disease (PD) is the second most common neurodegenerative disease, and the most common synucleinopathy, as alpha-synuclein (α-syn), plays an important pathophysiologic role in its onset and progression. The search for validated probes to visualize α-syn deposition could substantially advance efforts to establish a biological definition of synucleinopathies. However, current radiotracers have not demonstrated specific neuronal synuclein signal.

Method: 52 patients with clinically diagnosed PD and 9 healthy controls (HCs) underwent ¹⁸F-FD4 PET at Huashan Hospital, Fudan University. Images were analyzed visually and semi-quantitatively, and correlations with disease severity (UPDRS-III scores) were assessed. 2 patients also completed a second ¹⁸F-FD4 PET scan within 2 months after taking monoamine oxidase-B (MAO-B) inhibitor.

Results: ¹⁸F-FD4 PET revealed increased uptake in basal ganglia (especially anterior putamen), pons and raphe nucleus in patients with PD, compared to HCs. A significantly positive correlation was found between ¹⁸F-FD4 binding and UPDRS-III in anterior putamen and supplementary motor area. Longitudinal data confirms that there were no apparent pre- versus post- MAO-B inhibitor changes with respect to the patterns of ¹⁸F-FD4 uptake.

Conclusion: This study provides initial proof-of-concept for ¹⁸F-FD4 PET as an in vivo biomarker of α-syn pathology in PD, and supports the reliability of this imaging biomarker as an indicator of α-syn even in areas where α-syn and MAO-B colocalization would be expected.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18f-fd4-pet-reveals-%ce%b1-synuclein-deposition-and-clinical-correlations-in-parkinsons-disease/