DECREASED TUMOR OXYGENATION AFTER CYCLOPHOSPHAMIDE, REOXYGENATION ANDTHERAPEUTIC ENHANCEMENT WITH A PERFLUBRON EMULSION CARBOGEN BREATHING

Oxygen profiles of the rat mammary 13672 carcinoma were determined usi ng a pO2 histograph prior to treatment and 24 h and 48 h after i.p. ad ministration of a single dose of cyclophosphamide (300 mg/kg). The tum ors were severely hypoxic at 24 h post the administration of cyclophos phamide. There was little increase in oxygenation of the tumors at 48 h post therapy compared with 24 h post therapy indicating that reoxyge nation after cyclophosphamide was occurring very slowly in this tumor. Carbogen breathing improved the oxygenation of the tumors under each of the conditions studied. Administration of the perflubron emulsion ( 8 ml/kg) produced little or no change in the oxygenation of the tumors under normal air breathing conditions. However, the addition of carbo gen breathing to administration of the perflubron emulsion increased t he oxygenation of the tumors to levels equal to or greater than carbog en breathing at the mean/median pO2's. Perhaps most significantly, adm inistration of the perflubron emulsion with carbogen breathing increas ed the oxygenation of the most hypoxic regions of the tumors but carbo gen breathing alone did not. The growth delay of the Lewis lung carcin oma increased with increasing dose.of the perflubron emulsion along wi th cyclophosphamide (3 x 150 mg/kg) and carbogen breathing (6 h). This combination treatment was most effective when the cyclophosphamide wa s prepared in the perflubron emulsion. The number of lung metastases d ecreased in a manner parallel with increased efficacy of the treatment toward the primary tumor.