Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI.
Jordan BF, Misson P, Demeure R, Baudelet C, Beghein N, Gallez B
Laboratories of Medicinal Chemistry and Radiopharmacy, Universite Catholique de Louvain, Brussels, Belgium.
[Medline record in process]
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 pO(2) 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 pO(2)
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 pO(2) 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 pO(2) 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 pO(2), but as efficient as isosorbide dinitrate in the Gd-DTPA
contrast-enhanced imaging. We conclude that the effects of carbogen on
improving tumor pO(2) involve both improved blood flow and improved hemoglobin
oxygenation, whereas the effects of isosorbide dinitrate are predominantly
mediated by improved blood flow alone.
PMID: 10974477, UI: 20432159