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Positron Emission Tomography Imaging of Neuroinflammation
Open accessAbstract
In the diseased brain, upon activation microglia express binding sites for synthetic ligands designed to recognize the 18-kDa translocator protein TP-18, which is part of the so-called peripheral benzodiazepine receptor complex. PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide], the prototype synthetic ligand, has been widely used for the functional characterization of TP-18. Its cellular source in activated microglia has been established using high-resolution, single-cell autoradiography with the R-enantiomer [3H](R)-PK11195. Radiolabeled [11C](R)-PK11195 has been used to image active brain disease with positron emission tomography. Consistent with experimental and postmortem observations of a characteristically distributed pattern of microglia activation in areas of focal pathology, as well as in anterograde and retrograde projection areas, the in vivo regional [11C](R)-PK11195 signal is found in active focal lesions and over time also along the affected neural tracts and their respective cortical and subcortical projection areas. Thus, a profile of active disease emerges that matches some of the typical distribution patterns known from structural neuroimaging techniques, but additionally shows involvement of brain regions linked through neural pathways. In the context of cell-based in vivo neuropathology, the image data are thus best interpreted in the context of the emerging cellular understanding of brain disease or damage, rather than the definitions of clinical diagnosis. One important observation, borne out by experiment, is the long latency with which activated microglia or increased PK11195 retention appear to gradually emerge and remain in distal areas secondarily affected by disease, supporting speculations that the presence of activated microglia is an important corollary of brain plasticity.
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“Use of TSPO-binding radioligands to assess neuroinflammation via PET imaging indicates that they may have value as a biosensor of ongoing disease and may also be a target to reduce inflammation-mediated damage in diseases such as HIV-associated neurological disorders and dementia ([17] and see [15;18] for review).”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [15]
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“PET studies show that there is generally an increased retention of [11C]-PK11195 in various neurodegenerative conditions including HIV encephalitis (HIVE), and its simian model SIV encephalitis (SIVE), Alzheimer’s disease (AD), Huntington’s disease, multiple sclerosis (MS), Parkinson’s disease (PD), stroke, amyotrophic lateral sclerosis, and CNS neoplasms (see [14;15] for review).”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [15]
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“Traditional autoradiography studies of postmortem tissues confirm that TSPO binding sites are increased in many of these diseases and that these binding sites are primarily in microglia.”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [15]
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Metadata
- Authors
- Cagnin, A., Kassiou, M., Meikle, S. R., & Banati, R. B.
- Affiliations
- University of Padua (IT)
- The University of Sydney (AU)
- Corresponding author
- Cagnin, Annachiara
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 4
- Issue
- 3
- Pages
- 443-452
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC7479716
- OpenAlex
- W1996796928
- Cited by
- 137
- References
- 78
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 15 · 2014: 19 · 2013: 6 · 2012: 12
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- neuroinflammation, microglial activation, translocator protein (TSPO), PK11195, [11C]PK11195, positron emission tomography, focal brain lesions, neuroplasticity, neuropathology
- MeSH terms
- Animals, Brain, Brain Diseases, Carbon Radioisotopes, Humans, Inflammation, Isoquinolines, Microglia, Receptors, GABA, Radiopharmaceuticals, Positron-Emission Tomography
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