title: Increased tissue oxygenation and enhanced radiation sensitivity of solid tumors in rodents following polyethylene glycol conjugated bovine hemoglobin administration.
abstract: BACKGROUND
  Hypoxic tumors are frequently resistant to radiation therapy. Polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) was tested for its ability to increase oxygen tension in the hypoxic rat osteogenic sarcoma UMR-106, murine Lewis lung carcinoma LL2 and rat gliosarcoma 9L. In addition, PEG-Hb was tested as an adjunct for radiotherapy in UMR-106 and human prostate carcinoma PC-3 solid tumors.
  
  
  METHODS
  Rodents bearing established subcutaneous tumors were intravenously administered PEG-Hb. Tumor surface tissue oxygen tension was measured by both OxySpot and OxyMap systems, which utilize the same phosphorescence quenching method.
  
  
  RESULTS
  A time-dependent rise in oxygen tension was noted, and the maximum tissue oxygen tensions were observed two hours post PEG-Hb administration, and sustained for at least 2 hours. Following a single dose radiation of 4 Gray, osteogenic sarcoma tumors in the PEG-Hb treated group showed dramatic regression (complete remission occurred in 100% of the high dose PEG-Hb treated rats), as compared to control (Ringer's lactate) group tumors that showed continued aggressive growth. All PEG-Hb plus radiation treated animals bearing human prostate carcinoma (PC-3) showed significant tumor growth delay compared to both control (Ringer's lactate) and irradiation only treated animals.
  
  
  CONCLUSIONS
  PEG-Hb increased tumor oxygen content and improved the effectiveness of radiotherapy in these rodent models.
authors.affiliation: Enzon Inc., Piscataway, NJ 08854, USA.
authors.forename: R
authors.initials: R
authors.lastname: Linberg
authors.forename: C D
authors.initials: CD
authors.lastname: Conover
authors.forename: K L
authors.initials: KL
authors.lastname: Shum
authors.forename: R G
authors.initials: RG
authors.lastname: Shorr
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage; D002417:Cattle; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012516:Osteosarcoma / Q000378:metabolism* / Q000532:radiotherapy*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000378:metabolism* / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen