PET imaging of [11C]PBR28 in Parkinson's disease patients does not indicate increased binding to TSPO despite reduced dopamine transporter binding - PubMed (original) (raw)

PET imaging of [11C]PBR28 in Parkinson's disease patients does not indicate increased binding to TSPO despite reduced dopamine transporter binding

Katarina Varnäs et al. Eur J Nucl Med Mol Imaging. 2019 Feb.

Abstract

Purpose: To examine the hypothesis that cerebral binding to the 18 kDa translocator protein (TSPO), a marker of microglia activation, is elevated in Parkinson's disease (PD), and to assess the relationship between brain TSPO binding and dopaminergic pathology in PD.

Methods: The radioligand [11C]PBR28 was used for quantitative assessment of brain TSPO in 16 control subjects and 16 PD patients. To analyse the relationship between dopaminergic pathology and brain TSPO binding, PET studies of the dopamine transporter (DAT) were undertaken in PD patients using the DAT radioligand [18F]FE-PE2I. The total distribution volume of [11C]PBR28 was quantified in nigrostriatal regions, limbic cortices and thalamus, and the binding potential of [18F]FE-PE2I was quantified in nigrostriatal regions.

Results: Based on genotype analysis of the TSPO rs6971 polymorphism, 16 subjects (8 control subjects and 8 PD patients) were identified as high-affinity binders, and the remaining subjects were identified as mixed-affinity binders. A two-way ANOVA showed a strong main effect of TSPO genotype on the cerebral binding of [11C]PBR28, whereas no statistically significant main effect of diagnostic group, or a group by genotype interaction was found for any of the regions analysed. [18F]FE-PE2I PET studies in patients indicated a marked reduction in nigrostriatal binding to DAT. However, no correlations between the binding parameters were found for [11C]PBR28 and [18F]FE-PE2I.

Conclusion: The findings do not support the hypothesis of elevated cerebral TSPO binding or a relationship between TSPO binding and dopaminergic pathology in PD.

Keywords: 18 kDa translocator protein; Dopamine transporter; PET imaging; Parkinson’s disease.

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Conflict of interest statement

Conflicts of interest

The studies were supported by AstraZeneca. Dr. Cselényi, Dr. Jucaite and Prof. Farde are employees of AstraZeneca. Prof. Farde has served as a panel member for evaluation of the research programs of the Faculty of Medicine, University of Helsinki, Finland. The other authors declare no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1

Fig. 1

Average parametric images of [11C]PBR28 _V_T in control subjects (left) and PD patients (centre) and of [18F]FE-PE2I BPND in PD patients (right). The areas with high [11C]PBR28 _V_T represent binding in the thalamus

Fig. 2

Fig. 2

[11C]PBR28 _V_T values of selected brain regions in control subjects and PD patients. MAB mixed-affinity binder, HAB high-affinity binder

Fig. 3

Fig. 3

Correlations between [11C]PBR28 _V_T and [18F]FE-PE2I BPND in PD patients for the substantia nigra (top) and putamen (centre), and between [18F]FE-PE2I BPND for the putamen and [11C]PBR28 _V_T for the substantia nigra (bottom). MAB mixed-affinity binder, HAB high-affinity binder

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