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- Title
The translocator protein ligand [F]DPA-714 images glioma and activated microglia in vivo.
- Authors
Winkeler, Alexandra; Boisgard, Raphael; Awde, Ali; Dubois, Albertine; Thézé, Benoit; Zheng, Jinzi; Ciobanu, Luisa; Dollé, Frédéric; Viel, Thomas; Jacobs, Andreas; Tavitian, Bertrand
- Abstract
Purpose: In recent years there has been an increase in the development of radioligands targeting the 18-kDa translocator protein (TSPO). TSPO expression is well documented in activated microglia and serves as a biomarker for imaging neuroinflammation. In addition, TSPO has also been reported to be overexpressed in a number of cancer cell lines and human tumours including glioma. Here we investigated the use of [F]DPA-714, a new TSPO positron emission tomography (PET) radioligand to image glioma in vivo. Methods: We studied the uptake of [F]DPA-714 in three different rat strains implanted with 9L rat glioma cells: Fischer (F), Wistar (W) and Sprague Dawley (SD) rats. Dynamic [F]DPA-714 PET imaging, kinetic modelling of PET data and in vivo displacement studies using unlabelled DPA-714 and PK11195 were performed. Validation of TSPO expression in 9L glioma cell lines and intracranial 9L gliomas were investigated using Western blotting and immunohistochemistry of brain tissue sections. Results: All rats showed significant [F]DPA-714 PET accumulation at the site of 9L tumour implantation compared to the contralateral brain hemisphere with a difference in uptake among the three strains (F > W > SD). The radiotracer showed high specificity for TSPO as demonstrated by the significant reduction of [F]DPA-714 binding in the tumour after administration of unlabelled DPA-714 or PK11195. TSPO expression was confirmed by Western blotting in 9L cells in vitro and by immunohistochemistry ex vivo. Conclusion: The TSPO radioligand [F]DPA-714 can be used for PET imaging of intracranial 9L glioma in different rat strains. This preclinical study demonstrates the feasibility of employing [F]DPA-714 as an alternative radiotracer to image human glioma.
- Subjects
GLIOMAS; MICROGLIA; LIGANDS (Biochemistry); PROTEIN research; POSITRON emission tomography; BENZODIAZEPINE receptors
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2012, Vol 39, Issue 5, p811
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-011-2041-4