Journal article Open Access

[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


Dublin Core Export

<?xml version='1.0' encoding='utf-8'?>
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Boutin, Hervé</dc:creator>
  <dc:creator>Murray, Katie</dc:creator>
  <dc:creator>Pradillo, Jesus</dc:creator>
  <dc:creator>Maroy, Renaud</dc:creator>
  <dc:creator>Smigova, Alison</dc:creator>
  <dc:creator>Gerhard, Alexander</dc:creator>
  <dc:creator>Jones, Paul A</dc:creator>
  <dc:creator>Trigg, William</dc:creator>
  <dc:date>2014-10-29</dc:date>
  <dc:description>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.

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).

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 ± 0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BPND = 3.5 ± 0.4 and 2.4 ± 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 ± 5 % and 63 ± 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.

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.</dc:description>
  <dc:identifier>https://zenodo.org/record/15873</dc:identifier>
  <dc:identifier>10.1007/s00259-014-2939-8</dc:identifier>
  <dc:identifier>oai:zenodo.org:15873</dc:identifier>
  <dc:relation>info:eu-repo/grantAgreement/EC/FP7/278850/</dc:relation>
  <dc:relation>url:https://zenodo.org/communities/inmind</dc:relation>
  <dc:relation>url:https://zenodo.org/communities/ecfunded</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://creativecommons.org/licenses/by/4.0/legalcode</dc:rights>
  <dc:source>Eur J Nucl Med Mol Imaging 42(3) 503-11 (2014)</dc:source>
  <dc:subject>positron emission tomography</dc:subject>
  <dc:subject>translocator protein</dc:subject>
  <dc:subject> R-PK11195</dc:subject>
  <dc:subject>brain ischemia</dc:subject>
  <dc:subject>GE-180</dc:subject>
  <dc:title>[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>
20
20
views
downloads
Views 20
Downloads 20
Data volume 35.1 MB
Unique views 19
Unique downloads 20

Share

Cite as