Increased tissue oxygenation and enhanced radiation sensitivity of solid tumors in rodents following polyethylene glycol conjugated bovine hemoglobin administration.
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.
Linberg
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Enzon Inc., Piscataway, NJ 08854, USA.
Conover
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Shum
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Shorr
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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
D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen