Radiosensitization of hypoxic tumor cells by dodecafluoropentane: a gas-phase perfluorochemical emulsion.
One method to make hypoxic, radioresistant cells more radiation sensitive has been to increase the oxygen carrying capacity of normal blood using liquid perfluorochemical emulsions combined with breathing high pO2 gases. We investigated the ability of dodecafluoropentane (DDFP) to sensitize the moderately radiation-resistant Morris 7777 hepatoma based on our previous inability to modify the radiation response of this tumor. DDFP is used in very small quantities compared with perfluorchemicals reported previously. Rats under isoflurane anesthesia were administered EF5 3 h before irradiation to monitor the pretreatment level of tissue hypoxia. At -40 min, DDFP was administered i.v. at 3.5 ml/kg over 30 min. At -10 min, the rats were either continued with air (for controls) or switched to carbogen. The tumors were then irradiated and processed for evaluation of radiation response. Tumor-cell survival for DDFP treatment with air-breathing animals was not significantly different from controls treated without DDFP. Carbogen alone provided minimal sensitization. DDFP plus carbogen caused dramatic radiosensitization, and the radiation response of cells from these tumors was the same as a completely aerobic radiation response. DDFP plus carbogen appears to completely reverse the hypoxic cell radioresistance in this tumor model.
Koch
Cameron J
CJ
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA. kochc@mail.med.upenn.edu
Oprysko
Patricia R
PR
Shuman
A Lee
AL
Jenkins
W Timothy
WT
Brandt
Gordon
G
Evans
Sydney M
SM
D000818:Animals; D015687:Cell Hypoxia; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000532:radiotherapy*; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF; D010420:Pentanes
D005466:Fluorocarbons; D010100:Oxygen; D011838:Radiation-Sensitizing Agents; C008806:perfluoropentane; D010420:Pentanes