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[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.

Boutin, Hervé; Murray, Katie; Pradillo, Jesus; Maroy, Renaud; Smigova, Alison; Gerhard, Alexander; Jones, Paul A; Trigg, William


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{
  "description": "<p>PURPOSE: Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer 11C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer 18F-GE-180 in a rat model of stroke.</p>\n\n<p>METHODS: Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with 11C-R-PK11195 and 18F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP).</p>\n\n<p>RESULTS: 18F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of 11C-R-PK11195 uptake (1.5&thinsp;&plusmn;&thinsp;0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BPND&thinsp;=&thinsp;3.5&thinsp;&plusmn;&thinsp;0.4 and 2.4&thinsp;&plusmn;&thinsp;0.5 for 18F-GE-180 and 11C-R-PK11195, respectively, with R 1 = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180 significantly displaced 18F-GE-180 (69&thinsp;&plusmn;&thinsp;5 % and 63&thinsp;&plusmn;&thinsp;4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry.</p>\n\n<p>CONCLUSION: The in vivo binding characteristics of 18F-GE-180 demonstrate a better signal to noise ratio than 11C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in healthy tissue. These results provide evidence that 18F-GE-180 is a strong candidate to replace 11C-R-PK11195.</p>", 
  "license": "http://creativecommons.org/licenses/by/4.0/legalcode", 
  "creator": [
    {
      "affiliation": "Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK", 
      "@type": "Person", 
      "name": "Boutin, Herv\u00e9"
    }, 
    {
      "affiliation": "Faculty of Life Sciences, University of Manchester, Manchester, UK", 
      "@type": "Person", 
      "name": "Murray, Katie"
    }, 
    {
      "affiliation": "Faculty of Life Sciences, University of Manchester, Manchester, UK; Present address: Universidad Complutense/Politecnica de Madrid, Madrid, Spain", 
      "@type": "Person", 
      "name": "Pradillo, Jesus"
    }, 
    {
      "affiliation": "SHFJ - CEA Orsay, France", 
      "@type": "Person", 
      "name": "Maroy, Renaud"
    }, 
    {
      "affiliation": "Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK", 
      "@type": "Person", 
      "name": "Smigova, Alison"
    }, 
    {
      "affiliation": "Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK", 
      "@type": "Person", 
      "name": "Gerhard, Alexander"
    }, 
    {
      "affiliation": "GE Healthcare Ltd., Amersham, UK", 
      "@type": "Person", 
      "name": "Jones, Paul A"
    }, 
    {
      "affiliation": "GE Healthcare Ltd., Amersham, UK", 
      "@type": "Person", 
      "name": "Trigg, William"
    }
  ], 
  "url": "https://zenodo.org/record/15873", 
  "image": "https://zenodo.org/static/img/logos/zenodo-gradient-round.svg", 
  "datePublished": "2014-10-29", 
  "headline": "[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.", 
  "keywords": [
    "positron emission tomography", 
    "translocator protein", 
    " R-PK11195", 
    "brain ischemia", 
    "GE-180"
  ], 
  "@context": "https://schema.org/", 
  "identifier": "https://doi.org/10.1007/s00259-014-2939-8", 
  "@id": "https://doi.org/10.1007/s00259-014-2939-8", 
  "@type": "ScholarlyArticle", 
  "name": "[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke."
}
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