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Mov Disord. 2018 Apr;33(4):592-599. doi: 10.1002/mds.27316. Epub 2018 Feb 13.

Nigrostriatal dopamine transporter availability in early Parkinson's disease.

Author information

1
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
2
Department of Clinical Neuroscience, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
3
PET Science Centre, Precision Medicine and Genomics, Innovative Medicine & Early Development (IMED) Biotech Unit, AstraZeneca, Karolinska Institutet, Sweden.

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

PMID:
29436751
DOI:
10.1002/mds.27316

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