Distribution of WR-2721 in Normal and Malignant Tissues of Mice and Rats Bearing Solid Tumors: Dependence on Tumor Type, Drug Dose and Species

Abstract

WASHBURN, L. C., CARLTON, J. E., HAYES, R. L., AND YUHAS, J. M. Distribution of WR-2721 in Normal and Malignant Tissues of Mice and Rats Bearing Solid Tumors: Dependence on Tumor Type, Drug Dose and Species. Radiat. Res. 59, 475-483 (1974). S-2-[3-Aminopropylamino]ethylphosphorothioic acid (WR-2721) preferentially protects the normal, as opposed to the malignant, tissues of tumor-bearing mice from radiation injury. The major factor responsible for this difference in response appears to be the relatively poor absorption of the drug by the tumor. In order to determine whether deficient drug absorption was characteristic of solid tumors and to extend the study of the absorption patterns to the problems which might be encountered in clinical radiotherapy, normal and tumor tissue concentrations of 35S-labeled WR-2721 were determined 30 min after injection of graded doses of the drug (1, 50, 100, or 300 mg/kg) in two species (mice and rats) bearing 4 different solid tumors (P-1798 lymphosarcoma and CA-755 adenocarcinoma in mice and the RFT tumor and Morris 7777 hepatoma in rats). It has been demonstrated that: (1) 3 of the 4 tumors studied evidenced deficient drug absorption, but the Morris 7777 hepatoma absorbed WR-2721 as readily as the host's normal tissues; (2) the relative concentration of the drug in normal and tumor tissues was independent of the injected dose between 50 and 300 mg/kg; (3) the injection of tracer levels of WR-2721 (1 mg/kg) can be used to identify those tumors which show a deficient absorption, but not to quantitate the degree of this deficiency; and (4) the relationship between the injected dose and tissue concentration, after correction for species differences in surface area, was species independent for the lungs, small intestine and spleen, but species dependent for kidney and liver. We conclude therefore that WR-2721 is a promising agent for increasing the efficiency of solid tumor radiotherapy, but that each tumor must be considered individually.