Back to Search
Start Over
The translocator protein ligand [¹⁸F]DPA-714 images glioma and activated microglia in vivo.
- Source :
-
European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2012 May; Vol. 39 (5), pp. 811-23. Date of Electronic Publication: 2012 Jan 21. - Publication Year :
- 2012
-
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 [(18)F]DPA-714, a new TSPO positron emission tomography (PET) radioligand to image glioma in vivo.<br />Methods: We studied the uptake of [(18)F]DPA-714 in three different rat strains implanted with 9L rat glioma cells: Fischer (F), Wistar (W) and Sprague Dawley (SD) rats. Dynamic [(18)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.<br />Results: All rats showed significant [(18)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 [(18)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.<br />Conclusion: The TSPO radioligand [(18)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 [(18)F]DPA-714 as an alternative radiotracer to image human glioma.
- Subjects :
- Animals
Biological Transport
Cell Line, Tumor
Fluorine Radioisotopes
Gene Expression Regulation, Neoplastic
Glioma metabolism
Kinetics
Ligands
Mice
Microglia metabolism
Positron-Emission Tomography
Rats
Substrate Specificity
Glioma diagnostic imaging
Microglia diagnostic imaging
Pyrazoles metabolism
Pyrimidines metabolism
Receptors, GABA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1619-7089
- Volume :
- 39
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- European journal of nuclear medicine and molecular imaging
- Publication Type :
- Academic Journal
- Accession number :
- 22270507
- Full Text :
- https://doi.org/10.1007/s00259-011-2041-4