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Title: 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 preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. The authors hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. In the present study, the [alpha]/[beta] agonist ephedrine, the Ca[sup 2+] channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA [+-] carbogen antitumor effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both emulsion was given rapidly. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine 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 administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growthmore » delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. 45 refs., 4 figs.« less
Authors:
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Publication Date:
OSTI Identifier:
6936312
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States); Journal Volume: 26:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; EPHEDRINE; RADIOSENSITIVITY EFFECTS; FLUORINE COMPOUNDS; NEOPLASMS; RADIOTHERAPY; VASODILATORS; MICE; ALKALOIDS; AMINES; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; CARDIOVASCULAR AGENTS; DISEASES; DRUGS; HALOGEN COMPOUNDS; HYDROXY COMPOUNDS; MAMMALS; MEDICINE; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; RADIOLOGY; RODENTS; SYMPATHOMIMETICS; THERAPY; VASOCONSTRICTORS; VERTEBRATES 560152* -- Radiation Effects on Animals-- Animals