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.

• Authors: Patrik Fazio, Per Svenningsson, Zsolt Cselényi, Christer Halldin, Lars Farde, Andrea Varrone
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 33 Issue 4 Pg. 592-599 (04 2018) ISSN: 1531-8257 [Electronic] United States
• PMID: 29436751 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 International Parkinson and Movement Disorder Society.

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Estradiol
• 16-fluoroestradiol

Topics

• Aged
• Corpus Striatum (diagnostic imaging, drug effects, metabolism)
• Dopamine Plasma Membrane Transport Proteins (metabolism)
• Estradiol (analogs & derivatives, pharmacokinetics)
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neural Pathways (diagnostic imaging, drug effects)
• Parkinson Disease (diagnostic imaging)
• Positron-Emission Tomography
• Severity of Illness Index
• Substantia Nigra (diagnostic imaging, drug effects, metabolism)