Abstract
PurposeTo 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.MethodsThe 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.ResultsBased 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.ConclusionThe findings do not support the hypothesis of elevated cerebral TSPO binding or a relationship between TSPO binding and dopaminergic pathology in PD.
Highlights
Parkinson’s disease (PD) is a neurological condition characterized by degeneration of dopaminergic nigrostriatal neurons, and by the presence of cytoplasmic protein deposits in the affected neuronal pathways [1]
For confirmation of nigrostriatal pathology, PD patients were examined using the dopamine transporter (DAT) radioligand [18F]FE-PE2I. [18F]FE-PE2I binding was analysed by visual assessment of striatal DAT loss, and criteria for inclusion were the presence of asymmetrical decrease in striatal [18F]FE-PE2I binding according to the criteria reported in the literature [20, 21]
Time curves for the fraction of parent radioligand in plasma indicated a slower rate of metabolism in PD patients, with group differences reaching statistical significance (P < 0.05) for samples collected at 30, 40, 50 and 70 min after tracer injection (Supplementary Fig. S2)
Summary
Parkinson’s disease (PD) is a neurological condition characterized by degeneration of dopaminergic nigrostriatal neurons, and by the presence of cytoplasmic protein deposits in the affected neuronal pathways [1]. The 18 kDa translocator protein (TSPO), is known to be expressed in microglia cells, and can be quantified using PET and TSPO radioligands, and is a putative biomarker of neuroinflammation in vivo [5]. Among the TSPO PET radioligands developed, [11C]PK11195 has been the most. [11C]PK11195 shows low specific binding to TSPO, which limits its use in the assessment of brain microglia in vivo. For this reason, several new TSPO radioligands have been developed with improved signal to noise ratio, including [11C]PBR28, [11C]DPA713, [18F]FEPPA, and [11C]DAA1106 [6]
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