Measuring Dopamine Transporter Availability and Synaptic Density in Parkinson's Disease: A Dual-Tracer Positron...

¹⁸F-FE-PE2I is a highly selective dopamine transporter (DAT) positron emission tomography (PET) radioligand, whereas ¹¹C-UCB-J targets synaptic vesicle glycoprotein 2A (SV2A), enabling the assessment of synaptic density. Both tracers show significant alterations in Parkinson's disease (PD) in nigrostriatal regions. However, the extent of overlap between overall synaptic loss and dopaminergic denervation across different disease stages remains unclear.

To evaluate similarities and differences between patterns of DAT and SV2A binding in healthy controls (HC) and PD patients at different disease stages.

Thirty patients with PD (12 women, age: 65.8 ± 7.1 years) and thirteen HCs (7 women, age: 57.8 ± 5.4 years) underwent PET imaging with ¹⁸F-FE-PE2I and ¹¹C-UCB-J on separate days. Patients with PD were also stratified by disease duration into two subgroups (<3 years, n = 10; >6 years, n = 11). Binding potentials (BP_ND) were quantified in four regions of interest (ROIs): caudate, putamen, ventral striatum (VS), and substantia nigra (SN). Between-group differences in BP_ND were evaluated against HCs for each tracer, and correlations between ¹⁸F-FE-PE2I and ¹¹C-UCB-J BP_ND were evaluated.

In HCs, significant correlations were observed between caudate ¹⁸F-FE-PE2I and striatal ¹¹C-UCB-J BP_ND (caudate, putamen, VS). In PD (full cohort and longer-duration subgroup), significant correlations emerged between SN ¹¹C-UCB-J and striatal ¹⁸F-FE-PE2I. Percent differences between patients with PD and HCs with ¹⁸F-FE-PE2I and ¹¹C-UCB-J were similar only in the SN.

This study examined the relationship between DAT and overall synaptic density in nigrostriatal ROIs in PD using dual-tracer PET imaging, and there were distinct patterns that vary across disease stages. Understanding the interplay between dopaminergic and presynaptic degeneration in PD could enhance our knowledge of its pathophysiology and contribute to improve diagnosis. © 2025 International Parkinson and Movement Disorder Society.