THERAPEUTIC EFFECT OF INFUSED FLUOSOL-DA CARBOGEN WITH EPHEDRINE, FLUNARIZINE, OR NITROPRUSSIDE

The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in precl inical solid tumors when the emulsion was administered by i.v. bolus i njection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. Purpose: We hypothesized t hat an increase in tumor perfusion resulted when Fluosol-DA was admini stered rapidly. Methods and Materials: In the present study, the alpha /beta agonist ephedrine, the Ca2+ channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been teste d. Results: Ephedrine administration resulted in a decrease in the rad iation plus Fluosol-DA +/- carbogen antitumor effects in both the Lewi s lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine ad ministration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both tumor systems. Even with flunarizine administration Fluosol-DA delivered sl owly was less effective than when the emulsion was given rapidly. Flun arizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6- fold increase in response compared with 2.4-2.2-fold with Fluosol-DA a dministered by injection i.v. and carbogen breathing prior to and duri ng radiation therapy using growth delay of the Lewis lung carcinoma. T he effects of nitroprusside were complex. This drug had considerably m ore effect at 10 Gy than at higher radiation doses. Conclusion: These studies suggest that Fluosol-DA given by i.v. injection may increase t umor perfusion and that a drug like flunarizine may be beneficial if t he Fluosol-DA is administered slowly followed by carbogen breathing an d radiation therapy.