Increased PK11195 PET binding in the cortex of patients with MS correlates with disability
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OBJECTIVE: Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability. METHODS: Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29). RESULTS: Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS. CONCLUSIONS: Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM.
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Our observations raise questions about the interpretation of widespread TSPO PET signal in the cortical region as arising from cortical lesions, as opposed to meningeal or leukocortical inflammation.
“While populations of patients undoubtedly show heterogeneity of grey matter pathology, our observations here raise questions about the interpretation of widespread TSPO PET signal in the cortical region as arising from cortical lesions (Politis et al., 2012), as opposed to meningeal (Howell et al., 2011) or leukocortical inflammation.”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Politis et al., 2012
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- Authors
- Politis, M., Giannetti, P., Su, P., Turkheimer, F., Keihaninejad, S., Wu, K., Waldman, A., Malik, O., Matthews, P. M., Reynolds, R., Nicholas, R., & Piccini, P.
- Affiliations
- Hammersmith Hospital (GB)
- From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.),...
- ORCID
- Venue
- Neurology
- Published
- 2012-08-07
- Volume
- 79
- Issue
- 6
- Pages
- 523-530
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3413767
- OpenAlex
- W2148602027
- Cited by
- 176
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 9 · 2019: 15 · 2018: 13 · 2017: 15 · 2016: 19 · 2015: 21 · 2014: 19 · 2013: 7 · 2012: 5
- FWCI
- 12.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- multiple sclerosis, microglial activation, PK11195, [11C]PK11195 PET, cortical gray matter, disability, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, demyelination, Expanded Disability Status Scale, MSIS-29, postcentral gyrus, precentral gyrus
- MeSH terms
- Adult, Cerebral Cortex, Female, Humans, Isoquinolines, Male, Middle Aged, Multiple Sclerosis, Microglia, Radiopharmaceuticals, Positron-Emission Tomography
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