Dual Biomarker Potential of 18F-PR04.MZ-PET: Assessing Dopaminergic Function and Cerebral Blood Flow in Degenerative Parkinsonian Syndromes

Objective ¹⁸ F-PR04.MZ is a new PET radiopharmaceutical for the dopamine transporter (DAT), characterized by enhanced affinity and selectivity for this membrane protein. Previous investigations employing various radiotracers in dementia and movement disorders have suggested that R1 images, derived from compartmental analysis of dynamic studies, can serve as a proxy for cerebral blood flow (CBF). This study aims to evaluate the relationship between R1 values from dynamic ¹⁸ F-PR04.MZ studies as a proxy of CBF and brain glucose metabolism in patients with degenerative parkinsonisms (DP). Methods: Fifteen patients with DP (10 with Parkinson's disease, 4 with multiple system atrophy, and 1 with progressive supranuclear palsy) underwent PET/CT imaging with both, ¹⁸ F-FDG and ¹⁸ F-PR04.MZ. Additionally, 15 healthy controls (HC) who underwent PET/CT scans with ¹⁸ F-PR04.MZ were included in the study. Parametric R1 images were generated using compartmental analysis of dynamic ¹⁸ F-PR04.MZ studies via the Simplified Reference Tissue Model (SRTM). Specific Uptake Index (SUI) were calculated to assess dopaminergic integrity in both patients and HC. Comparisons of SUI values between the two groups were performed, and the correlation between R1 and brain glucose metabolism was analyzed across cortical and subcortical regions. Results: DP patients exhibited significantly lower SUI values for the caudate (11.5 ± 3.2), putamen (8.6 ± 3.9), and substantia nigra (1.5 ± 0.9) compared to HC (17.9 ± 2.9, 22.3 ± 3.1, and 4.7 ± 1.4, respectively; p < 0.001 for all regions). A strong correlation was identified between R1 values derived from ¹⁸ F-PR04.MZ studies and brain metabolism in various regions, including the putamen (correlation coefficient [CC] 0.82), caudate nuclei (CC 0.73), parietal (CC 0.68), occipital (CC 0.63), frontal (CC 0.69), and temporal cortex (CC 0.82, p<0.001 for all comparisons). Conclusion: R1 images derived from dynamic ¹⁸ F-PR04.MZ studies offer promising insights into CBF changes in cortical and subcortical regions affected by DP. This strategy holds potential as a tool in the differential diagnosis of DP.