Biodistribution of the radioprotective drug ³⁵S-labeled 3-amino-2-hydroxypropyl phosphorothioate (WR77913)

3-Amino-2-hydroxypropyl phosphorothioate (WR77913), a less toxic phosphorothioate radioprotector than WR2721, has been labeled with ³⁵S. The biodistribution of a radioprotective dose of 800 mg/kg was determined in C3H mice bearing RIF-1 tumors as a function of time after intraperitoneal injection and was expressed as percentage injected dose/gram (% ID/g). Levels of ³⁵S in the blood peaked 10 min after injection, and radioactivity in most tissues was highest at 15 min. Label in most tissues declined markedly between 15 and 60 min, but in gut, salivary glands, tumor, and brain, the levels of radioactivity remained quite stable over 1 hr. At 30 min after injection the highest levels of labeled drug were found in submandibular salivary glands, gut, and kidney, with the lowest level in brain. Tumors had approximately the same amount of label as blood, muscle, skin, and esophagus. Two principal differences between the distribution of label from WR77913 and WR2721 were defined. Although blood levels of ³⁵S-WR2721 also peaked 10 min after injection, the 10-min blood levels achieved for WR77913 were more than fourfold greater than those attained by WR2721. Maximum levels of WR2721 occurred in most tissues 30 to 60 min after administration of the drug, compared to 15 min for WR77913. The basis for these differences remains to be determined, but these results suggest than the optimum interval between administration of WR77913 and irradiation may be shorter than for WR2721.