²³⁸Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice

Abstract

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 ²³⁸Pu 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 ²³⁸Pu elimination enhancement after delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation agent under development.

Keywords::

• Alpha emitters
• plutonium
• radiation protection
• radionuclides
• medical countermeasures
• chelation therapy

Acknowledgements

This work was supported by the Biomedical Advanced Research and Development Authority (BARDA, Contract #IPIAA12OS99609) at the E. O. Lawrence Berkeley National Laboratory, a U.S. Department of Energy Laboratory under Contract No. DE-AC02-05CH11231.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.