title: The translocator protein ligand [¹⁸F]DPA-714 images glioma and activated microglia in vivo.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Inserm, U1023, Laboratoire d'Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.forename: Raphael
authors.initials: R
authors.lastname: Boisgard
authors.forename: Ali R
authors.initials: AR
authors.lastname: Awde
authors.forename: Albertine
authors.initials: A
authors.lastname: Dubois
authors.forename: Benoit
authors.initials: B
authors.lastname: Thézé
authors.forename: Jinzi
authors.initials: J
authors.lastname: Zheng
authors.forename: Luisa
authors.initials: L
authors.lastname: Ciobanu
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D051379:Mice; D017628:Microglia / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005462:Fluorine Radioisotopes; D008024:Ligands; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human