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.


OBJECTIVE
We hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly.


METHODS
In the present study, the alpha/beta agonist ephedrine, the Ca2+ channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested.


RESULTS
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 tumor systems. 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 growth 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.


CONCLUSIONS
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.
Teicher
B A
BA
Dana-Farber Cancer Institute, Boston, MA.
Holden
S A
SA
Northey
D
D
Dewhirst
M W
MW
Herman
T S
TS
D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D004809:Ephedrine / Q000627:therapeutic use*; D005444:Flunarizine / Q000627:therapeutic use*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000627:therapeutic use*; D006895:Hydroxyethyl Starch Derivatives; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009599:Nitroprusside / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009599:Nitroprusside; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; C011700:carbogen; D004809:Ephedrine; D005444:Flunarizine; D010100:Oxygen