Decreased tumor oxygenation after cyclophosphamide, reoxygenation and therapeutic enhancement with a perflubron emulsion carbogen breathing.

Oxygen profiles of the rat mammary 13672 carcinoma were determined using a pO2 histograph prior to treatment and 24 h and 48 h after i.p. administration of a single dose of cyclophosphamide (300 mg/kg). The tumors were severely hypoxic at 24 h post the administration of cyclophosphamide. There was little increase in oxygenation of the tumors at 48 h post therapy compared with 24 h post therapy indicating that reoxygenation 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 carbogen breathing to administration of the perflubron emulsion increased the oxygenation of the tumors to levels equal to or greater than carbogen breathing at the mean/median pO2's. Perhaps most significantly, administration of the perflubron emulsion with carbogen breathing increased the oxygenation of the most hypoxic regions of the tumors but carbogen breathing alone did not. The growth delay of the Lewis lung carcinoma increased with increasing dose.of the perflubron emulsion along with cyclophosphamide (3 x 150 mg/kg) and carbogen breathing (6 h). This combination treatment was most effective when the cyclophosphamide was prepared in the perflubron emulsion. The number of lung metastases decreased in a manner parallel with increased efficacy of the treatment toward the primary tumor.