Efaproxiral, an allosteric modifier of
hemoglobin, reduces
hemoglobin-
oxygen binding affinity, facilitating
oxygen release from
hemoglobin, which is likely to increase tissue pO(2). The purpose of this study was to determine the effect of
efaproxiral on
tumor oxygenation and growth inhibition of RIF-1
tumors that received X radiation (4 Gy) plus
oxygen breathing compared to radiation plus
oxygen plus
efaproxiral daily for 5 days. Two
lithium phthalocyanine (LiPc) deposits were implanted in RIF-1
tumors in C3H mice for
tumor pO(2) measurements using EPR oximetry.
Efaproxiral significantly increased
tumor oxygenation by 8.4 to 43.4 mmHg within 5 days, with maximum increases at 22-31 min
after treatment.
Oxygen breathing alone did not affect
tumor pO(2). Radiation plus
oxygen plus
efaproxiral produced
tumor growth inhibition throughout the
treatment duration, and inhibition was significantly different from radiation plus
oxygen from day 3 to day 5. The results of this study provide unambiguous quantitative information on the effectiveness of
efaproxiral to consistently and reproducibly increase
tumor oxygenation over the course of 5 days of treatment, modeling the clinical use of
efaproxiral. Also, based on the
tumor growth inhibition, the study shows the
efaproxiral-enhanced
tumor oxygenation was radiobiologically significant. This is the first study to demonstrate the ability of
efaproxiral to increase
tumor oxygenation and to increase the
tumor growth inhibition of
radiotherapy over 5 days of treatment.