Reduced oxygenation in a rat mammary carcinoma after chemo- or radiation therapy and reoxygenation with perflubron emulsion/carbogen breathing.
Rat 13672 mammary carcinoma tumors were grown subcutaneously in the hind legs of female Fischer 344 rats to a volume of about 1 cm3. Tumor oxygenation was measured using an Eppendorf PO2 histograph. Tumor oxygen measurements were made under four conditions: (a) normal air breathing, (b) carbogen breathing, (c) after intravenous administration of a perflubron emulsion (8 ml/kg) with air breathing and (d) after intravenous administration of a perflubron emulsion (8 ml/kg) with carbogen breathing. Tumor oxygenation was examined without treatment or 24 h and 48 h after treatment with cyclophosphamide (300 mg/kg, i.p.) or cisplatin (8 mg/kg, i.p.] or after the fifth dose of a daily regimen of 3-Gy irradiation (5 x 3 Gy). Under normal air-breathing conditions 49% of the tumor had a PO2 < or = 670 Pa (5 mm Hg). The degree of hypoxia in the tumors increased after each treatment such that 24 h after treatment 65%-85% of the oxygen readings were < or = 670 Pa and 48 h after treatment 60%-74% of the oxygen readings were < or = 670 Pa. Administration of the perflubron emulsion/carbogen atmosphere increased the oxygen content of the tumors both without treatment and after each of the treatments. A knowledge of tumor oxygen content over the course of treatment and the ability to increase tumor oxygen should allow for the development of more rational treatment combinations and better treatment outcomes.
Teicher
B A
BA
Dana-Farber Cancer Institute, Boston, MA.
Sotomayor
E A
EA
Dupuis
N P
NP
Kusumoto
T
T
Menon
K
K
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002945:Cisplatin / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D006842:Hydrocarbons, Brominated; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D010100:Oxygen / Q000032:analysis* / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D003520:Cyclophosphamide; C003072:perflubron; D002945:Cisplatin; D010100:Oxygen