Tissue
oxygen tensions were measured in subcutaneously growing rat 9L
gliosarcoma under normal air and
carbogen breathing conditions prior to and after i.v. administration of a
perflubron emulsion. When these animals were treated with the anti-angiogenic agents
TNP-470 and
minocycline for 5 days prior to
oxygen measurement, tumor hypoxia was decreased compared with untreated
tumors.
Hypoxia, defined as the percent of pO2 readings < or = 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the
perflubron emulsion and
carbogen breathing. These effects were manifest in the increased response of the
tumor to single-dose (10, 20 and 30 Gy) radiation
therapy. Twenty-four hours
after treatment with
BCNU oxygenation of the
tumors was not altered; however, 24 hr after administration of
adriamycin oxygenation of the
tumors was increased such that
hypoxia in
adriamycin-treated
tumors in animals receiving the
perflubron emulsion and
carbogen was reduced to 21%.
Tumor growth delay in the s.c.
tumors was increased by the addition of treatment with the anti-angiogenic agents from day 4 through day 18 post-
tumor cell implantation along with
BCNU or
adriamycin on days 7-11. Administration of the
perflubron emulsion and
carbogen breathing resulted in increased
tumor growth delay with the chemotherapeutic agents alone and in combination with the anti-angiogenic agents. Life span in animals bearing intracranially implanted 9L
gliosarcoma progressively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and
perflubron emulsion/
carbogen compared to treatment with
BCNU or
adriamycin.