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Cited by 138Neuroinflammation and Neurodegeneration MechanismsMedical Imaging Techniques and ApplicationsPharmacological Receptor Mechanisms and Effects

Positron Emission Tomography Imaging of Neuroinflammation

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Cagnin, Annachiara, Kassiou, Michael, Meikle, Steve R., Banati, Richard B.·2007·Neurotherapeutics
DOI 10.1016/j.nurt.2007.04.006PMC PMC7479716
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Abstract

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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  • TSPO-binding radioligands used to assess neuroinflammation via PET imaging 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.

    “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]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • PET studies show generally increased retention of [11C]-PK11195 in various neurodegenerative conditions including HIVE, SIVE, AD, Huntington's disease, MS, PD, stroke, ALS, and CNS neoplasms.

    “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]

    The Dementia, Movement disorders, Multiple sclerosis, and Stroke sections report increased [11C](R)-PK11195 binding or PET signal in AD, Huntington’s disease, PD, MS, and stroke. The passages found do not report PET findings for HIVE, SIVE, ALS, or CNS neoplasms, so the full list is not supported by this source. Page numbers were not supplied in our copy. (LLM, conf=0.88)

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  • Traditional autoradiography studies of postmortem tissues confirm that TSPO binding sites are increased in many neurodegenerative diseases and that these binding sites are primarily in microglia.

    “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]

    The Cellular source and function section (page unavailable) reports that microautoradiography finds increased PK11195 binding predominantly on activated microglia, though it also identifies binding on infiltrating blood-borne cells. The Dementia and Movement disorders sections describe increased binding in several neurodegenerative diseases, but chiefly from in vivo PET studies; the paper does not establish that postmortem autoradiography confirmed those increases across many such diseases. (LLM, conf=0.85)

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Cites

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3 of the 78 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Hertz L. Binding characteristics of the receptor and coupling to transport proteins. In: Giessen-Crouse E, editor. Peripheral benzo- diazepine receptors. London: Academic Press, 1993:27-51.
  2. Banati RB, Goerres GW, Myers R, Gunn RN, Turkheimer FE, Kreutzberg GW, et al. [ 11 C](R)-PK11195 PET-imaging of acti- vated microglia in vivo in Rasmussen's encephalitis. Neurology 1999;53:2199 -2203.
  3. Rasmussen T, Andermann F. Rasmussen's syndrome: symptom- atology of the syndrome of chronic encephalitis and seizures: 35-year experience with 51 cases. In: Lüders H, editor. Epilepsy surgery, 1st ed. New York: Raven Press, 1991:173-182.

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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
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2007-07
Volume
4
Issue
3
Pages
443-452
ISSN
1878-7479 (ISSN-L)
DOI
10.1016/j.nurt.2007.04.006
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
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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