title: (238)Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Chemical Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, California , USA.
authors.forename: Dahlia D
authors.initials: DD
authors.lastname: An
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Villalobos
authors.forename: Joel A
authors.initials: JA
authors.lastname: Morales-Rivera
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Bjornstad
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Gauny
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Choi
authors.forename: Manuel
authors.initials: M
authors.lastname: Sturzbecher-Hoehne
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Abergel
mesh_terms: D000818:Animals; D001822:Body Burden; D002614:Chelating Agents / Q000737:chemistry; D015913:Chelation Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D007668:Kidney / Q000528:radiation effects; D008099:Liver / Q000528:radiation effects; D008297:Male; D051379:Mice; D011005:Plutonium / Q000009:adverse effects* / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry* / Q000627:therapeutic use; D012737:Sex Factors; D013997:Time Factors
chemical_list: C000594124:1,5,10,14-tetra(1-hydroxy-2-pyridon-6-oyl)-1,5,10,14-tetraazatetradecane; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D011728:Pyridones; D011005:Plutonium; C546958:1-hydroxy-2(1H)-pyridinone
keywords: Alpha emitters; chelation therapy; medical countermeasures; plutonium; radiation protection; radionuclides