Purpose: To characterize the dose-dependent and sex-related efficacy of the hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium elimination when post-exposure treatment is delayed.
Materials and methods: Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 μmol/kg were evaluated for decorporating plutonium in female and male Swiss-Webster mice administered a soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the female groups and at three time-points (2, 4, and 8 days post-contamination) for the male groups.
Results: Elimination enhancement was dose-dependent in the 1-100 μmol/kg dose range at all necropsy time-points, with some significant reductions in full body and tissue content for both female and male animals. The highest dose level resulted in slight toxicity, with a short recovery period, which delayed excretion of the radionuclide.
Conclusions: While differences were noted between the female and male cohorts in efficacy range and recovery times, all groups displayed sustained dose-dependent (238)Pu elimination enhancement after delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation agent under development.
Keywords: Alpha emitters; chelation therapy; medical countermeasures; plutonium; radiation protection; radionuclides.