title: Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma.
abstract: Despite multiple advances in cancer therapies, patients with glioblastoma (GBM) still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a reliable method to map hypoxia in preclinical human models may contribute to the discovery and translation of future and more targeted therapies. The aim of this study was to compare the hypoxic status of two commonly used human orthotopic glioma models (U87 and U251) developed in rats and studied by noninvasive hypoxia imaging with 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol-micro-positron emission tomography ([18F]-FMISO-μPET). In parallel, because of the relationships between angiogenesis and hypoxia, we used magnetic resonance imaging (MRI), histology, and immunohistochemistry to characterize the tumoral vasculature. Although all tumors were detectable in T2-weighted MRI and 2-deoxy-2-[18F]fluoro-d-glucose-μPET, only the U251 model exhibited [18F]-FMISO uptake. Additionally, the U251 tumors were less densely vascularized than U87 tumors. Our study demonstrates the benefits of noninvasive imaging of hypoxia in preclinical models to define the most reliable one for translation of future therapies to clinic based on the importance of intratumoral oxygen tension for the efficacy of chemotherapy and radiotherapy.
authors: Aurélien
authors: A
authors: Corroyer-Dulmont
authors: Elodie A
authors: EA
authors: Pérès
authors: Edwige
authors: E
authors: Petit
authors: Lucile
authors: L
authors: Durand
authors: Léna
authors: L
authors: Marteau
authors: Jérôme
authors: J
authors: Toutain
authors: Didier
authors: D
authors: Divoux
authors: Simon
authors: S
authors: Roussel
authors: Eric T
authors: ET
authors: MacKenzie
authors: Louisa
authors: L
authors: Barré
authors: Myriam
authors: M
authors: Bernaudin
authors: Samuel
authors: S
authors: Valable
mesh_terms: D005910:Glioma / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008920:Misonidazole / Q000031:analogs & derivatives*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: C031843:fluoromisonidazole; D008920:Misonidazole