Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme'

Abstract

Tumor-cell hypoxia is one of the main factors inducing radioresistance. Enhanced tumor oxygenation has previously been achieved in an animal model using the synthetic heme-based oxygen carrier 'albumin-heme' (recombinant human serum albumin-Fe cyclohexanoil heme; rHSA-FeP). The present study was done to determine whether rHSA-FeP enhances the radiation response in an experimental tumor model. Male Donryu rats and LY80, a variant of the syngenic liver ascites tumor, were used. A total of 1 × 106 cells were injected into the subfascial tissue of the right thigh. The rats were divided randomly into five groups: sham (tumor implantation and sham operation); rHSA-FeP; irradiation; rHSA + irradiation; and rHSA-FeP + irradiation. Six days after, under general anesthesia, intra-arterial administration of 10 mL/ kg of either 5% rHSA solution or oxygenated rHSA-FeP solution at 2.5 mL/ min was done and a dose of 20 Gy was given. There were significant differences in tumor growth between the sham and irradiation groups, and between the sham and rHSA-FeP + irradiation groups. Tumor growth delay was observed and differences were significant between the sham and irradiation groups, and between the irradiation and rHSA-FeP + irradiation groups. In the present study, rHSA-FeP itself had a slight effect on tumor growth without irradiation. Enhancing the effect of rHSA-FeP on the radiation response is responsible in part for the oxygen-carrying property of rHSA-FeP. In conclusion, rHSA-FeP is a candidate radiation-enhancing drug. Arterial infusion of rHSA-FeP may serve as a local oxygenation method that enhances the radiation effect. © 2008 Japanese Cancer Association.