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

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. Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 μmol/kg were evaluated for decorporati...

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Bibliographic Details
Published in:International journal of radiation biology 2014-11, Vol.90 (11), p.1055
Main Authors: An, Dahlia D, Villalobos, Jonathan A, Morales-Rivera, Joel A, Rosen, Chris J, Bjornstad, Kathleen A, Gauny, Stacey S, Choi, Taylor A, Sturzbecher-Hoehne, Manuel, Abergel, Rebecca J
Format: Article
Language:English
Subjects:
Animals
Body Burden
Chelating Agents - chemistry
Chelation Therapy - methods
Dose-Response Relationship, Drug
Female
Heterocyclic Compounds, 1-Ring - chemistry
Kidney - radiation effects
Liver - radiation effects
Male
Mice
Plutonium - adverse effects
Plutonium - chemistry
Pyridones - chemistry
Pyridones - therapeutic use
Sex Factors
Time Factors
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Summary: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. 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. 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. 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.
ISSN:1362-3095
DOI:10.3109/09553002.2014.925150