title: Validation of an engineered cell model for in vitro and in vivo HIF-1α evaluation by different imaging modalities.
abstract: OBJECTIVE
  The aim of this study was to characterize a cell-based model for the molecular study of hypoxia-inducible factor (HIF)-1α activity, in the context of hypoxia, by means of different imaging techniques.
  
  
  METHODS
  Engineered U251-HRE glioma cells were used to analyze the molecular mechanisms underlying HIF-1α activity in vitro in relation to luciferase expression. The same cells were orthotopically implanted in mice to evaluate tumor progression and hypoxia induction by bioluminescence imaging, fluorescence imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI).
  
  
  RESULTS
  In vitro analyses highlighted the relationship between HIF-1α and luciferase activity in hypoxic conditions and after pharmacological treatments in U251-HRE cells. Through in vivo studies, it was possible to assess hypoxia establishment in relation to tumor growth by optical imaging, PET and MRI.
  
  
  CONCLUSIONS
  The findings of this study indicate that the U251-HRE orthotopic murine model can be used to reliably evaluate processes modulating HIF-1α activity, using both molecular and preclinical non-invasive imaging techniques.
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lo Dico
authors.forename: S
authors.initials: S
authors.lastname: Valtorta
authors.forename: C
authors.initials: C
authors.lastname: Martelli
authors.forename: S
authors.initials: S
authors.lastname: Belloli
authors.forename: U
authors.initials: U
authors.lastname: Gianelli
authors.forename: D
authors.initials: D
authors.lastname: Tosi
authors.forename: S
authors.initials: S
authors.lastname: Bosari
authors.forename: A
authors.initials: A
authors.lastname: Degrassi
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.forename: I
authors.initials: I
authors.lastname: Raccagni
authors.forename: G
authors.initials: G
authors.lastname: Lucignani
authors.forename: R M
authors.initials: RM
authors.lastname: Moresco
authors.forename: L
authors.initials: L
authors.lastname: Ottobrini
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008954:Models, Biological; D064847:Multimodal Imaging / Q000379:methods*; D061848:Optical Imaging; D049268:Positron-Emission Tomography; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases; D003676:Deferoxamine