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In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naive Young Adults with Major Depression: A [¹¹C]PK11195 PET Study.

ABSTRACT: Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [¹¹C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [¹¹C]PK11195 PET. We quantified TSPO availability in brain as the [¹¹C]PK11195 binding potential (BP_ND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [¹¹C]PK11195 BP_ND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [¹¹C]PK11195 BP_ND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [¹¹C]PK11195 BP_ND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.

SUBMITTER: Joo YH

PROVIDER: S-EPMC8773340 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeNeuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [(18)F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [(18)F]DPA-714, it was compared directly to [(11)C]PK11195 in experimental cerebral ischaemia in rats.MethodsUnder anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [(11)C]PK11195 and/or [(18)F]DPA-714 under anaesthesia.ResultsUptake of [(11)C]PK11195 vs [(18)F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [(11)C]PK11195 or with [(18)F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [(11)C]PK11195 and [(18)F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [(11)C]PK11195 vs [(18)F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [(18)F]DPA-714.ConclusionsIn a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [(18)F]DPA-714 displayed a higher signal-to-noise ratio than [(11)C]PK11195. Our results suggest that, with the longer half-life of [(18)F] which facilitates distribution of the tracer across PET centre, [(18)F]DPA-714 is a good alternative for TSPO imaging.

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In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naive Young Adults with Major Depression: A [¹¹C]PK11195 PET Study.

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In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naive Young Adults with Major Depression: A [11C]PK11195 PET Study.

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OmicsDI is part of the ELIXIR infrastructure

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In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naive Young Adults with Major Depression: A [¹¹C]PK11195 PET Study.