• In vivo · Mar 1998

    Increased tissue oxygenation and enhanced radiation sensitivity of solid tumors in rodents following polyethylene glycol conjugated bovine hemoglobin administration.

    • R Linberg, C D Conover, K L Shum, and R G Shorr.
    • Enzon Inc., Piscataway, NJ 08854, USA.
    • In Vivo. 1998 Mar 1;12(2):167-73.

    BackgroundHypoxic 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 MethodsRodents 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.ResultsA 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.ConclusionPEG-Hb increased tumor oxygen content and improved the effectiveness of radiotherapy in these rodent models.

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