PII S0360-3016(00)00694-5 BIOLOGY CONTRIBUTION CHANGES IN TUMOR OXYGENATION/PERFUSION INDUCED BY THE NO DONOR, ISOSORBIDE DINITRATE, IN COMPARISON WITH CARBOGEN: MONITORING BY EPR AND MRI

Purpose: In an effort to improve radiotherapy treatments, methods aimed at increasing the quantity of oxygen delivered to tumors were investigated. The aim of this study was to evaluate the effect of one nitric oxide (NO) donor (isosorbide dinitrate) on pO2 and blood flow in a murine tumor model. The effect was compared to carbogen, used as a reference treatment. Methods and Materials: Thirty-six liver tumors implanted in mouse thighs were imaged using magnetic resonance imaging (MRI) at 4.7 Tesla with dynamic Gd-DTPA and blood oxygen level-dependent (BOLD) contrast-enhanced imaging after administration of isosorbide dinitrate or carbogen. The effect on the pO2 was also tested by EPR oximetry (1.1 GHz) on 52 mice. Results: A significant increase in MRI intensity was observed for both treatments in comparison with the control group. EPR oximetry showed a dose-dependant increase in tumor pO2 for isosorbide dinitrate (by 5.9 mmHg at 0.2 mg/kg) and a substantially greater change for carbogen breathing (by 23 mmHg). Conclusion: Both tumor blood flow and pO2 were increased by isosorbide dinitrate and carbogen. Carbogen is more efficient than isosorbide dinitrate in increasing the BOLD image intensity, as well as the tumor pO2, but as efficient as isosorbide dinitrate in the Gd-DTPA contrast-enhanced imaging. We conclude that the effects of carbogen on improving tumor pO2 involve both improved blood flow and improved hemoglobin oxygenation, whereas the effects of isosorbide dinitrate are predominantly mediated by improved blood flow alone. © 200