title: The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma.
abstract: OBJECTIVE
  To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT).
  
  
  METHODS
  Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy × 10 with 3-min pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, (18)F-fluorodeoxyglucose (FDG) (tumor metabolism), and (18)F-fluoromisonidazole (FMISO) (hypoxia) positron emission tomography (PET) imaging before, at midpoint, and after treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology.
  
  
  RESULTS
  UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared with UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia after SRT when compared with PRT as measured by (18)F-FMISO PET. By contrast, no differences were seen in (18)F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histologic analysis of pimonidazole staining mimicked the (18)F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors.
  
  
  CONCLUSIONS
  Differences in (18)F-FMISO uptake for UT14 tumors after radiation therapy between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by (18)F-FMISO and pimonidazole.
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wobb
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Krueger
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kane
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Sandra
authors.initials: S
authors.lastname: Galoforo
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Inga S
authors.initials: IS
authors.lastname: Grills
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan. Electronic address: brian.marples@beaumont.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D064593:Heterografts; D051379:Mice; D008819:Mice, Nude; D008920:Misonidazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009364:Neoplasm Recurrence, Local; D009593:Nitroimidazoles; D010101:Oxygen Consumption / Q000528:radiation effects*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D047368:Tumor Burden / Q000528:radiation effects
chemical_list: D004396:Coloring Agents; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; C033815:pimonidazole; D008920:Misonidazole