Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG

Sara Belloli, Andrea Brioschi, Letterio Salvatore Politi, Francesca Ronchetti, Sara Calderoni, Isabella Raccagni, Antonella Pagani, Cristina Monterisi, Francesco Zenga, Gianpaolo Zara, Ferruccio Fazio, Alessandro Mauro, Rosa Maria Moresco

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Abstract

Introduction: 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, [18F]FDG- and [18F]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 [18F]FAZA and high-glucose metabolism regions recognized with [18F]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 [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]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.

Original languageEnglish
Pages (from-to)831-840
Number of pages10
JournalNuclear Medicine and Biology
Volume40
Issue number6
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Fluorodeoxyglucose F18
Glioblastoma
Glioma
Disease Progression
Neoplasms
Immunohistochemistry
Multimodal Imaging
Image-Guided Radiotherapy
Nestin
Biological Models
Environmental Monitoring
Delayed Diagnosis
Inbred F344 Rats
Vascular Endothelial Growth Factor A
Cell Count
Pathology
Glucose
fluoroazomycin arabinoside
Brain

Keywords

  • GBM model
  • Glucose metabolism
  • Hypoxia
  • Immunohistochemistry
  • MRI
  • PET

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Characterization of biological features of a rat F98 GBM model : A PET-MRI study with [18F]FAZA and [18F]FDG. / Belloli, Sara; Brioschi, Andrea; Politi, Letterio Salvatore; Ronchetti, Francesca; Calderoni, Sara; Raccagni, Isabella; Pagani, Antonella; Monterisi, Cristina; Zenga, Francesco; Zara, Gianpaolo; Fazio, Ferruccio; Mauro, Alessandro; Moresco, Rosa Maria.

In: Nuclear Medicine and Biology, Vol. 40, No. 6, 08.2013, p. 831-840.

Research output: Contribution to journalArticle

Belloli, S, Brioschi, A, Politi, LS, Ronchetti, F, Calderoni, S, Raccagni, I, Pagani, A, Monterisi, C, Zenga, F, Zara, G, Fazio, F, Mauro, A & Moresco, RM 2013, 'Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG', Nuclear Medicine and Biology, vol. 40, no. 6, pp. 831-840. https://doi.org/10.1016/j.nucmedbio.2013.05.004
Belloli, Sara ; Brioschi, Andrea ; Politi, Letterio Salvatore ; Ronchetti, Francesca ; Calderoni, Sara ; Raccagni, Isabella ; Pagani, Antonella ; Monterisi, Cristina ; Zenga, Francesco ; Zara, Gianpaolo ; Fazio, Ferruccio ; Mauro, Alessandro ; Moresco, Rosa Maria. / Characterization of biological features of a rat F98 GBM model : A PET-MRI study with [18F]FAZA and [18F]FDG. In: Nuclear Medicine and Biology. 2013 ; Vol. 40, No. 6. pp. 831-840.
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abstract = "Introduction: 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, [18F]FDG- and [18F]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 [18F]FAZA and high-glucose metabolism regions recognized with [18F]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 [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]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.",
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T1 - Characterization of biological features of a rat F98 GBM model

T2 - A PET-MRI study with [18F]FAZA and [18F]FDG

AU - Belloli, Sara

AU - Brioschi, Andrea

AU - Politi, Letterio Salvatore

AU - Ronchetti, Francesca

AU - Calderoni, Sara

AU - Raccagni, Isabella

AU - Pagani, Antonella

AU - Monterisi, Cristina

AU - Zenga, Francesco

AU - Zara, Gianpaolo

AU - Fazio, Ferruccio

AU - Mauro, Alessandro

AU - Moresco, Rosa Maria

PY - 2013/8

Y1 - 2013/8

N2 - Introduction: 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, [18F]FDG- and [18F]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 [18F]FAZA and high-glucose metabolism regions recognized with [18F]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 [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]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.

AB - Introduction: 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, [18F]FDG- and [18F]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 [18F]FAZA and high-glucose metabolism regions recognized with [18F]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 [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]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.

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KW - Immunohistochemistry

KW - MRI

KW - PET

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