[18F]FE-PE2I PET: a novel biomarker for Parkinson’s disease

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Current therapeutic options for idiopathic Parkinson’s disease (PD) offer a predominantly symptomatic treatment but cannot halt the progressive neurodegeneration. For the evaluation of new disease-modifying therapies, such as monoclonal antibodies targeting alpha-synuclein, adequate biomarkers that can detect subtle neuroprotective effects on a cellular level are urgently needed. [18F]FE-PE2I is a novel diagnostic agent for positron emission tomography (PET), which binds to the dopamine transporter (DAT). Recent studies showed its ability to precisely evaluate the neurodegeneration of dopamine-producing neurons. Beside the integrity of striatal nerve terminals, it also visualizes the whole nigro-striatal pathway including the cell bodies in, and the tracts and axons originating from the substantia nigra and thus, reveals information about the sequence of neuronal cell loss.This project aims to assess two outcome measures of [18F]FE-PE2I binding to the DAT: (i) the non-displaceable binding potential (BPND), which requires a high-resolution PET system and a dynamic brain scan over 93 min, and (ii) the specific binding ratio (SBR), which is a simplified quantification method and can be obtained with an acquisition time of just 26 min on a standard clinical PET scanner. BPND will be estimated via wavelet-aided parametric imaging for signal-to-noise reduction and Logan graphical analysis; the SBR will be calculated based on static images with a simulated resolution of a clinical PET system. The assessment of both measures will involve three aspects. (i) Test-retest reliability of [18F]FE-PE2I PET measures in a cohort of 10 PD patients. (ii) Longitudinal validity describing the decline of [18F]FE-PE2I binding along with PD progression in a subset of 15 PD patients (mean follow-up of 2 years). (iii) Comparison of [18F]FE-PE2I binding values in 40 healthy controls and 40 PD patients (de novo, early and advanced disease stage) and correlation of BPND with SBR, demographic and clinical parameters (e.g. age, disease duration, motor (sub-)scores, and non-motor symptoms). The reproducibility in a single subject, cross-sectional and follow-up data have not yet been examined for [18F]FE-PE2I PET. This project will show the suitability of [18F]FE-PE2I binding as a surrogate biomarker for disease progression, paving the way for more extensive use in clinical and research settings.