title: Hypoxia is important in the biology and aggression of human glial brain tumors.
abstract: We investigated whether increasing levels of tissue hypoxia, measured by the binding of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] or by Eppendorf needle electrodes, were associated with tumor aggressiveness in patients with previously untreated glial brain tumors. We hypothesized that more extensive and severe hypoxia would be present in tumor cells from patients bearing more clinically aggressive tumors. Hypoxia was measured with the 2-nitroimidazole imaging agent EF5 in 18 patients with supratentorial glial neoplasms. In 12 patients, needle electrode measurements were made intraoperatively. Time to recurrence was used as an indicator of tumor aggression and was analyzed as a function of EF5 binding, electrode values and recursive partitioning analysis (RPA) classification. On the basis of EF5 binding, WHO grade 2 tumors were characterized by modest cellular hypoxia (pO2s approximately 10%) and grade 3 tumors by modest-to-moderate hypoxia (pO2s approximately 10%- 2.5%). Severe hypoxia (approximately 0.1% oxygen) was present in 5 of 12 grade 4 tumors. A correlation between more rapid tumor recurrence and hypoxia was demonstrated with EF5 binding, but this relationship was not predicted by Eppendorf measurements.
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA. sydevans@mail.med.upenn.edu
authors.forename: Sydney M
authors.initials: SM
authors.lastname: Evans
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Judy
authors.forename: Isolde
authors.initials: I
authors.lastname: Dunphy
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Jenkins
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lustig
authors.forename: Kevin
authors.initials: K
authors.lastname: Jenkins
authors.forename: Deirdre P
authors.initials: DP
authors.lastname: Magarelli
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Collins
authors.forename: M Sean
authors.initials: MS
authors.lastname: Grady
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Koch
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D004566:Electrodes; D017341:Etanidazole / Q000031:analogs & derivatives / Q000378:metabolism; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007202:Indicators and Reagents; D008875:Middle Aged; D009339:Needles; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D013997:Time Factors; D005466:Fluorocarbons
chemical_list: D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons