title: Characterization of biological features of a rat F98 GBM model: a PET-MRI study with [18F]FAZA and [18F]FDG.
abstract: BACKGROUND
  The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry.
  
  
  METHODS
  Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [(18)F]FDG- and [(18)F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin.
  
  
  RESULTS
  Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [(18)F]FAZA and high-glucose metabolism regions recognized with [(18)F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [(18)F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [(18)F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy.
  
  
  CONCLUSIONS
  In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression.
authors.affiliation: IBFM-CNR, Segrate, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Belloli
authors.forename: Andrea
authors.initials: A
authors.lastname: Brioschi
authors.forename: Letterio Salvatore
authors.initials: LS
authors.lastname: Politi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronchetti
authors.forename: Sara
authors.initials: S
authors.lastname: Calderoni
authors.forename: Isabella
authors.initials: I
authors.lastname: Raccagni
authors.forename: Antonella
authors.initials: A
authors.lastname: Pagani
authors.forename: Cristina
authors.initials: C
authors.lastname: Monterisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Zenga
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zara
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mauro
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D051381:Rats; D016019:Survival Analysis
chemical_list: D009593:Nitroimidazoles; D019788:Fluorodeoxyglucose F18; C498052:fluoroazomycin arabinoside
keywords: GBM model; Glucose metabolism; Hypoxia; Immunohistochemistry; MRI; PET