Dataset Information

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

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.

SUBMITTER: Varnas K

PROVIDER: S-EPMC6333720 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Varnäs Katarina K Cselényi Zsolt Z Jucaite Aurelija A Halldin Christer C Svenningsson Per P Farde Lars L Varrone Andrea A

European journal of nuclear medicine and molecular imaging 20181001 2

<h4>Purpose</h4>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.<h4>Methods</h4>The radioligand [<sup>11</sup>C]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 bindi ...[more]

PMID: 30270409

Similar Datasets

Project description:Alzheimer's disease is associated with chronic response of innate immune system, referred as neuroinflammation. PET radioligands binding to the 18 kDa translocator protein are potential biomarkers of neuroinflammation. Translocator protein PET studies in mild cognitive impairment and Alzheimer's disease have indicated controversial results, possibly reflecting interindividual variation and heterogeneity of study populations. We controlled for genetic and environmental effects by studying twin pairs discordant for episodic memory performance. Episodic memory impairment is a well-known cognitive hallmark of early Alzheimer's disease process. Eleven same-sex twin pairs (four monozygotic pairs, six female pairs, age 72-77 years) underwent [11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28) PET imaging, structural magnetic resonance imaging and neuropsychological testing in 2014-17. Main PET outcome was the volume-weighted average standardized uptake value of cortical regions vulnerable to Alzheimer's disease pathology. Ten pairs were discordant for episodic memory performance. In the eight pairs with identical translocator protein genotype, twins with poorer episodic memory had ∼20% higher cortical [11C]PBR28 binding compared with their better-performing co-twins (mean intra-pair difference 0.21 standardized uptake value, 95% confidence interval 0.05-0.37, P = 0.017). The result remained the same when including all discordant pairs and controlling for translocator protein genotype. Increased translocator protein PET signal suggests that increased microglial activation is associated with poorer episodic memory performance. Twins with worse episodic memory performance compared with their co-twins had on average 20% higher uptake of the neuroinflammatory marker translocator protein PET tracer 11[11C]PBR28. The findings support a negative association between neuroinflammation and episodic memory and the use of translocator protein positron emission tomography as a useful indicator of Alzheimer's disease process.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets