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.

MATERIAL AND 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.

CONCLUSION:

PEG-Hb increased tumor oxygen content and improved the effectiveness of radiotherapy in these rodent models.

• Authors: R Linberg, C D Conover, K L Shum, R G Shorr
• Journal: In vivo (Athens, Greece) (In Vivo) 1998 Mar-Apr Vol. 12 Issue 2 Pg. 167-73 ISSN: 0258-851X [Print] Greece
• PMID: 9627798 (Publication Type: Journal Article)

Chemical References

• Blood Substitutes
• Hemoglobins
• PEG-hemoglobin
• Polyethylene Glycols
• Oxygen

Topics

• Animals
• Blood Substitutes (administration & dosage)
• Cattle
• Female
• Hemoglobins (administration & dosage)
• Humans
• Injections, Intravenous
• Male
• Mice
• Mice, Inbred C57BL
• Mice, SCID
• Osteosarcoma (metabolism, radiotherapy)
• Oxygen (metabolism)
• Oxygen Consumption (drug effects)
• Polyethylene Glycols (administration & dosage)
• Prostatic Neoplasms (metabolism, radiotherapy)
• Radiation Tolerance (drug effects)
• Rats
• Rats, Inbred F344
• Rats, Nude
• Rats, Sprague-Dawley
• Sarcoma, Experimental (metabolism, radiotherapy)
• Tumor Cells, Cultured