Distribution of³⁵ S-Labeled WR-2721 in Normal and Malignant Tissues of the Mouse

The radioprotective drug, WR-2721, labeled with³⁵ S, has been evaluated for distribution in BALB/c mice bearing the${\rm EMT}_{6}$ mouse mammary tumor. At 6, 20, and 60 min after intravenous injection the animals were sacrificed and autoradiographs were made from sagittal sections taken through the entire animal. Radioactivity was high in bone marrow, intestinal mucosa, and skin, which correlates with the radioprotection produced by this drug in these organs. An initial high level in the kidney fell rapidly over the time period studied, suggesting rapid excretion of the drug by the kidneys. The${\rm EMT}_{6}$ tumor had a low concentration with only minimal increase over the 60-min period, which also correlates with the low level of radioprotection demonstrated in this tumor by WR-2721. Low levels were seen in muscle, lung, and peripheral blood while essentially no uptake occurred in the brain. The liver showed a persistent high level of radiolabeled drug uptake and the submandibular salivary gland contained the highest concentration of any organ of the body at 1 hr. This suggests the possibility of protection of these two normal structures, which could have great clinical significance in radiation therapy.