Restoration of Tumor Oxygenation After Cytotoxic Therapy by A Perflubron Emulsion/Carbogen Breathing

Female, Fisher 344 rats bearing 13762 mammary carcinoma implanted subcutaneously in a hind limb were treated with standard therapeutic single doses of antitumor treatments of several types including: 1) antitumor alkylating agents (cisplatin, cyclophosphamide); 2) natural products (adriamycin, taxol and etoposide); 3) antimetabolites (5-flourouracil); 4) hypoxic cell selective agents (mitomycin C, SR-4233) as well as 5) fractionated radiation therapy (3 Gray daily for 5 days). The oxygen levels in the tumors were measured in the absence of treatment and 24 hrs. after treatment using an Eppendorf p02 histograph. Fifty- to sixty-points were measured per tumor and 8-10 tumors comprised each group. The tumors were more hypoxic post treatment with every anticancer drug or radiation. The percent of p02 readings < or = 5 mmHg in the untreated tumors ranged from 85% (x-rays) to 59% (etoposide). Administration of the perflubron emulsion (8 ml/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the tumors such that the percent of pO2 readings < or = 5 mmHg was 32% in the untreated controls and ranged from 27% (x-rays) to 56% (adria) in the treated tumors. These results indicate that administration of a perflubron emulsion/carbogen can increase the oxygen content of tumors when hypoxia is the result of cytotoxic therapy.