title: Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation.
abstract: OBJECTIVE
  Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [(18)F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation.
  
  
  METHODS
  [(18)F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation.
  
  
  RESULTS
  [(18)F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [(18)F]DPA-714 binding is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer and inflammation in mice did not show significant lesion-to-background signal ratios. Slower [(18)F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species.
  
  
  CONCLUSIONS
  Although TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.
authors.affiliation: Inserm U1023, Laboratoire d'Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, France. jinzi.zheng@rmp.uhn.on.ca.|CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, Orsay, France. jinzi.zheng@rmp.uhn.on.ca.|Techna Institute, University Health Network, 101 College Street, Room 7-302, Toronto, Ontario, Canada, M5G 1L7. jinzi.zheng@rmp.uhn.on.ca.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. jinzi.zheng@rmp.uhn.on.ca.
authors.forename: Jinzi
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Inserm U1023, Laboratoire d'Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, France.|CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.affiliation: CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Peyronneau
authors.affiliation: CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Inserm U1023, Laboratoire d'Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, France. raphael.boisgard@cea.fr.|CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, Orsay, France. raphael.boisgard@cea.fr.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Boisgard
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C463819:Bzrp protein, mouse; D002352:Carrier Proteins; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C069997:Tspo protein, rat
keywords: Cancer; DPA-714; Inflammation; PET imaging; TSPO