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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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  "doi": "10.2967/jnumed.113.125625", 
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    "latest_html": "https://zenodo.org/record/8583", 
    "doi": "https://doi.org/10.2967/jnumed.113.125625", 
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  "created": "2015-02-02T16:49:35+00:00", 
  "updated": "2020-01-20T15:15:20.181783+00:00", 
  "conceptrecid": "642668", 
  "revision": 11, 
  "id": 8583, 
  "metadata": {
    "access_right_category": "danger", 
    "doi": "10.2967/jnumed.113.125625", 
    "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>", 
    "title": "Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.", 
    "journal": {
      "volume": "55", 
      "year": "2014", 
      "issue": "3", 
      "pages": "466-72", 
      "title": "J Nucl Med."
    }, 
    "relations": {
      "version": [
        {
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          "index": 0, 
          "parent": {
            "pid_type": "recid", 
            "pid_value": "642668"
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    "communities": [
      {
        "id": "inmind"
      }, 
      {
        "id": "ecfunded"
      }, 
      {
        "id": "zenodo"
      }
    ], 
    "grants": [
      {
        "code": "278850", 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::278850"
        }, 
        "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", 
        "acronym": "INMIND", 
        "program": "FP7", 
        "funder": {
          "doi": "10.13039/501100000780", 
          "acronyms": [], 
          "name": "European Commission", 
          "links": {
            "self": "https://zenodo.org/api/funders/10.13039/501100000780"
          }
        }
      }
    ], 
    "keywords": [
      "neuroinflammation", 
      "positron emission tomography", 
      "second-generation TSPO ligand", 
      "brain", 
      "astrocyte"
    ], 
    "publication_date": "2014-02-10", 
    "creators": [
      {
        "affiliation": "Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland and MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
        "name": "Dickens, Alex M"
      }, 
      {
        "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
        "name": "Vainio, Susanne"
      }, 
      {
        "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
        "name": "Marjam\u00e4ki, P\u00e4ivi"
      }, 
      {
        "affiliation": "Turku PET Centre, University of Turku, Turku, Finland", 
        "name": "Johansson, Jarkko"
      }, 
      {
        "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
        "name": "Lehtiniemi, Paula"
      }, 
      {
        "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
        "name": "Rokka, Johanna"
      }, 
      {
        "affiliation": "Turku PET Centre, University of Turku, Turku, Finland", 
        "name": "Rinne, Juha"
      }, 
      {
        "affiliation": "Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku PET Centre, Turku, Finland", 
        "name": "Solin, Olof"
      }, 
      {
        "affiliation": "MediCity/PET Preclinical Laboratory, University of Turku, Turku, Finland", 
        "name": "Haaparanta-Solin, Merja"
      }, 
      {
        "affiliation": "GE Healthcare Ltd., Amersham, United Kingdom", 
        "name": "Jones, Paul A"
      }, 
      {
        "affiliation": "GE Healthcare Ltd., Amersham, United Kingdom", 
        "name": "Trigg, William"
      }, 
      {
        "affiliation": "Department of Pharmacology, University of Oxford, Oxford, United Kingdom", 
        "name": "Anthony, Daniel C"
      }, 
      {
        "affiliation": "Department of Neurology, Turku University Hospital, Turku, Finland", 
        "name": "Airas, Laura"
      }
    ], 
    "access_right": "closed", 
    "resource_type": {
      "subtype": "article", 
      "type": "publication", 
      "title": "Journal article"
    }
  }
}
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