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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", 
  "container_title": "J Nucl Med.", 
  "title": "Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180.", 
  "issued": {
    "date-parts": [
      [
        2014, 
        2, 
        10
      ]
    ]
  }, 
  "abstract": "<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>", 
  "author": [
    {
      "given": "Alex M", 
      "family": "Dickens"
    }, 
    {
      "given": "Susanne", 
      "family": "Vainio"
    }, 
    {
      "given": "P\u00e4ivi", 
      "family": "Marjam\u00e4ki"
    }, 
    {
      "given": "Jarkko", 
      "family": "Johansson"
    }, 
    {
      "given": "Paula", 
      "family": "Lehtiniemi"
    }, 
    {
      "given": "Johanna", 
      "family": "Rokka"
    }, 
    {
      "given": "Juha", 
      "family": "Rinne"
    }, 
    {
      "given": "Olof", 
      "family": "Solin"
    }, 
    {
      "given": "Merja", 
      "family": "Haaparanta-Solin"
    }, 
    {
      "given": "Paul A", 
      "family": "Jones"
    }, 
    {
      "given": "William", 
      "family": "Trigg"
    }, 
    {
      "given": "Daniel C", 
      "family": "Anthony"
    }, 
    {
      "given": "Laura", 
      "family": "Airas"
    }
  ], 
  "page": "466-72", 
  "volume": "55", 
  "type": "article-journal", 
  "issue": "3", 
  "id": "8583"
}
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