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Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.

Dickens, Alex M; Vainio, Susanne; Marjamäki, Päivi; Johansson, Jarkko; Lehtiniemi, Paula; Rokka, Johanna; Rinne, Juha; Solin, Olof; Haaparanta-Solin, Merja; Jones, Paul A; Trigg, William; Anthony, Daniel C; Airas, Laura


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{
  "description": "<p>It remains unclear how different translocator protein (TSPO) ligands reflect the spatial extent of astrocyte or microglial activation in various neuroinflammatory conditions. Here, we use a reproducible lipopolysaccharide (LPS)-induced model of acute central nervous system inflammation to compare the binding performance of a new TSPO ligand (18)F-GE-180 with (11)C-(R)-PK11195. Using immunohistochemistry, we also explore the ability of the TSPO ligands to detect activated microglial cells and astrocytes.</p>\n\n<p>METHODS: Lewis rats (n = 30) were microinjected with LPS (1 or 10 &mu;g) or saline (1 &mu;L) into the left striatum. The animals were imaged in vivo at 16 h after the injection using PET radiotracers (18)F-GE-180 or (11)C-(R)-PK11195 (n = 3 in each group) and were killed afterward for autoradiography of the brain. Immunohistochemical assessment of OX-42 and glial fibrillary acidic protein (GFAP) was performed to identify activated microglial cells and reactive astrocytes.</p>\n\n<p>RESULTS: In vivo PET imaging revealed an increase in the ipsilateral TSPO binding, compared with binding in the contralateral hemisphere, after the microinjection of 10 &mu;g of LPS. No increase was observed with vehicle. By autoradiography, the TSPO radiotracer binding potential in the injected hemisphere was increased after striatal injection of 1 or 10 &mu;g of LPS. However, the significant increase was observed only when using (18)F-GE-180. The area of CD11b-expressing microglial cells extended beyond that of enhanced GFAP staining and mapped more closely to the extent of (18)F-GE-180 binding than to (11)C-(R)-PK11195 binding. The signal from either PET ligand was significantly increased in regions of increased GFAP immunoreactivity and OX-42 colocalization, meaning that the presence of both activated microglia and astrocytes in a given area leads to increased binding of the TSPO radiotracers.</p>\n\n<p>CONCLUSION: (18)F-GE-180 is able to reveal sites of activated microglia in both gray and white matter. However, the signal is increased by the presence of activated astrocytes. Therefore, (18)F-GE-180 is a promising new fluorinated longer-half-life tracer that reveals the presence of activated microglia in a manner that is superior to (11)C-(R)-PK11195 due to the higher binding potential observed for this ligand.</p>", 
  "creator": [
    {
      "affiliation": "Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland and MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Dickens, Alex M"
    }, 
    {
      "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Vainio, Susanne"
    }, 
    {
      "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Marjam\u00e4ki, P\u00e4ivi"
    }, 
    {
      "affiliation": "Turku PET Centre, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Johansson, Jarkko"
    }, 
    {
      "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
      "@type": "Person", 
      "name": "Lehtiniemi, Paula"
    }, 
    {
      "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
      "@type": "Person", 
      "name": "Rokka, Johanna"
    }, 
    {
      "affiliation": "Turku PET Centre, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Rinne, Juha"
    }, 
    {
      "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
      "@type": "Person", 
      "name": "Solin, Olof"
    }, 
    {
      "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
      "@type": "Person", 
      "name": "Haaparanta-Solin, Merja"
    }, 
    {
      "affiliation": "GE Healthcare Ltd., Amersham, United Kingdom", 
      "@type": "Person", 
      "name": "Jones, Paul A"
    }, 
    {
      "affiliation": "GE Healthcare Ltd., Amersham, United Kingdom", 
      "@type": "Person", 
      "name": "Trigg, William"
    }, 
    {
      "affiliation": "Department of Pharmacology, University of Oxford, Oxford, United Kingdom", 
      "@type": "Person", 
      "name": "Anthony, Daniel C"
    }, 
    {
      "affiliation": "Department of Neurology, Turku University Hospital, Turku, Finland", 
      "@type": "Person", 
      "name": "Airas, Laura"
    }
  ], 
  "headline": "Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.", 
  "image": "https://zenodo.org/static/img/logos/zenodo-gradient-round.svg", 
  "datePublished": "2014-02-10", 
  "url": "https://zenodo.org/record/8583", 
  "keywords": [
    "neuroinflammation", 
    "positron emission tomography", 
    "second-generation TSPO ligand", 
    "brain", 
    "astrocyte"
  ], 
  "@context": "https://schema.org/", 
  "identifier": "https://doi.org/10.2967/jnumed.113.125625", 
  "@id": "https://doi.org/10.2967/jnumed.113.125625", 
  "@type": "ScholarlyArticle", 
  "name": "Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180."
}
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