title: Detection of hypoxia in human squamous cell carcinoma by EF5 binding.
abstract: Localization and quantitation of 2-nitroimidazole drug binding in low pO2 tumors is a technique that can allow the assessment of hypoxia as a predictive assay. EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] is such a drug, and it has been shown to be predictive of radiation response in rodent tumors. Using fluorescence immunohistochemical techniques, we provide data on the presence, distribution, and levels of EF5 binding as a surrogate for hypoxia in human head and neck and uterine cervix squamous cell cancers (SCCs). Six patients with SCC were studied. Four patients had head and neck tumors, and two had uterine cervix cancers. The incubation of fresh tissue cubes in EF3 under hypoxic conditions ("reference binding") demonstrated that all tumors were capable of binding drug, and that this binding varied by a factor of 2.9-fold (174.5-516.1) on an absolute fluorescence scale. In the five patients treated at the lowest drug doses (9 mg/kg), in situ binding was quantitatable. For all six patients, the maximum rate of in situ binding varied by a factor of 6.7 between the lowest and highest binding tumor (24.8-160.3) on an absolute fluorescence scale. In tumors with high binding regions, intratumoral heterogeneity was large, extending from minimal fluorescence (<1%) up to 88.6% of reference binding. In tumors with minimal binding, there was little intratumoral heterogeneity. These studies demonstrate substantial heterogeneity of in situ binding between and within individual squamous cell tumors.
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA. sydevans@vet.upenn.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Hahn
authors.forename: D R
authors.initials: DR
authors.lastname: Pook
authors.forename: W T
authors.initials: WT
authors.lastname: Jenkins
authors.forename: A A
authors.initials: AA
authors.lastname: Chalian
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Stevens
authors.forename: R
authors.initials: R
authors.lastname: Weber
authors.forename: G
authors.initials: G
authors.lastname: Weinstein
authors.forename: I
authors.initials: I
authors.lastname: Benjamin
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: M
authors.initials: M
authors.lastname: Morgan
authors.forename: S
authors.initials: S
authors.lastname: Rubin
authors.forename: W G
authors.initials: WG
authors.lastname: McKenna
authors.forename: E M
authors.initials: EM
authors.lastname: Lord
authors.forename: C J
authors.initials: CJ
authors.lastname: Koch
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D015687:Cell Hypoxia; D017341:Etanidazole / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005466:Fluorocarbons
chemical_list: D000970:Antineoplastic Agents; D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons