Nigrostriatal dopamine transporter availability in early Parkinson's disease

Abstract

Background: The imaging of biomarkers for characterization of dopaminergic impairment in Parkinson's disease (PD) is useful for diagnosis, patient stratification, and assessment of treatment outcomes. [¹⁸ F]FE-PE2I is an improved imaging tool allowing for detailed mapping of the dopamine transporter protein in the nigro-striatal system at the level of cell bodies (substantia nigra), axons, and presynaptic terminals (striatum).

Objectives: The objective of this study was to compare the dopamine transporter protein loss in the presynaptic terminals to that in the cell bodies and axons in early PD patients using [¹⁸ F](E)-N-(3-iodoprop-2-enyl)-2b-carbofluoroethoxy-3b-(4'-methyl-phenyl) nortropane ([¹⁸ F]FE-PE2I) and high-resolution PET.

Methods: A total of 20 early PD patients (15 men/5 women, 62 ± 8 years) and 20 controls (15 men/5 women, 62 ± 7 years) underwent high-resolution [¹⁸ F]FE-PE2I PET. Dopamine transporter protein availability was estimated for the different nigro-striatal regions and expressed as nondisplaceable binding potential values.

Results: When compared with controls, the binding potential values in PD patients were reduced by 36% to 70% in presynaptic terminals and by 30% in cell bodies. Dopamine transporter availability along the tracts was not different between the 2 groups (controls 0.5 ± 0.1 vs PD 0.4 ± 0.1).

Conclusions: This is the first study that examines dopamine transporter protein availability in vivo within the entire nigro-striatal pathway. The results suggest that at early stages of symptomatic PD a greater loss is observed at the level of the axonal terminals when compared with cell bodies and axons of dopaminergic neurons. The findings suggest a relative preservation of cell bodies in early PD, which might be relevant for novel disease-modifying strategies. © 2018 International Parkinson and Movement Disorder Society.

Keywords: PET imaging; Parkinson's disease; dopamine transporter protein (DAT); nigro-striatal degeneration; substantia nigra.