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Title: From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents

Abstract

The potential consequences of a major radiological event are not only large-scale external radiation exposure of the population, but also uncontrolled dissemination of, and internal contamination with, radionuclides. When planning an emergency response to radiological and nuclear incidents, one must consider the need for not only post-exposure treatment for contaminated individuals, but also prophylactic measures to protect the workforce facing contaminated areas and patients in the aftermath of such events. In addition to meeting the desired criteria for post-exposure treatments such as safety, ease of administration, and broad-spectrum efficacy against multiple radionuclides and levels of challenge, ideal prophylactic countermeasures must include rapid onset; induce minimal to no performance-decrementing side effects; be compatible with current military Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and require minimal logistical burdens. Hydroxypyridinone-based actinide decorporation agents have shown the most promise as decorporation strategies for various radionuclides of concern, including the actinides plutonium and americium. The studies here probe the extent of plutonium decorporation efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), from early pre-exposure time points to a delay of up to 7 days in parenteral or oral treatment administration, i.e., well beyond the initial hours of emergency response. Despite delayed treatment after amore » contamination event, both ligands clearly enhanced plutonium elimination through the investigated 7-day post-treatment period. In addition, a remarkable prophylactic efficacy was revealed for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.« less

Authors:
 [1];  [1];  [1];  [1]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
SC-22.1 USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division; National Institutes of Health (NIH)
OSTI Identifier:
1458488
Alternate Identifier(s):
OSTI ID: 1397624
Grant/Contract Number:  
AC02-05CH11231; RAI087604Z
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Chemico-Biological Interactions
Additional Journal Information:
Journal Volume: 267; Journal Issue: C; Related Information: © 2016 Elsevier Ireland Ltd; Journal ID: ISSN 0009-2797
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
61 RADIATION PROTECTION AND DOSIMETRY; Radionuclides; Contamination; Medical countermeasure; Chelation therapy; Prophylaxis

Citation Formats

An, Dahlia D., Kullgren, Birgitta, Jarvis, Erin E., and Abergel, Rebecca J. From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents. United States: N. p., 2016. Web. doi:10.1016/j.cbi.2016.03.034.
An, Dahlia D., Kullgren, Birgitta, Jarvis, Erin E., & Abergel, Rebecca J. From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents. United States. doi:10.1016/j.cbi.2016.03.034.
An, Dahlia D., Kullgren, Birgitta, Jarvis, Erin E., and Abergel, Rebecca J. Thu . "From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents". United States. doi:10.1016/j.cbi.2016.03.034. https://www.osti.gov/servlets/purl/1458488.
@article{osti_1458488,
title = {From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents},
author = {An, Dahlia D. and Kullgren, Birgitta and Jarvis, Erin E. and Abergel, Rebecca J.},
abstractNote = {The potential consequences of a major radiological event are not only large-scale external radiation exposure of the population, but also uncontrolled dissemination of, and internal contamination with, radionuclides. When planning an emergency response to radiological and nuclear incidents, one must consider the need for not only post-exposure treatment for contaminated individuals, but also prophylactic measures to protect the workforce facing contaminated areas and patients in the aftermath of such events. In addition to meeting the desired criteria for post-exposure treatments such as safety, ease of administration, and broad-spectrum efficacy against multiple radionuclides and levels of challenge, ideal prophylactic countermeasures must include rapid onset; induce minimal to no performance-decrementing side effects; be compatible with current military Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and require minimal logistical burdens. Hydroxypyridinone-based actinide decorporation agents have shown the most promise as decorporation strategies for various radionuclides of concern, including the actinides plutonium and americium. The studies here probe the extent of plutonium decorporation efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), from early pre-exposure time points to a delay of up to 7 days in parenteral or oral treatment administration, i.e., well beyond the initial hours of emergency response. Despite delayed treatment after a contamination event, both ligands clearly enhanced plutonium elimination through the investigated 7-day post-treatment period. In addition, a remarkable prophylactic efficacy was revealed for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.},
doi = {10.1016/j.cbi.2016.03.034},
journal = {Chemico-Biological Interactions},
issn = {0009-2797},
number = C,
volume = 267,
place = {United States},
year = {2016},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
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Cited by: 7 works
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Figures / Tables:

Fig. 1. Fig. 1.: Total 238Pu body content and distribution at 7 days after a single time-delayed ip chelation treatment. Young adult female Swiss-Webster mice injected iv with 238Pu-citrate; saline or treatment (3,4,3-LI(1,2-HOPO) [30 mmol/kg], 5-LIO(Me-3,2-HOPO) [100 mmol/kg], or Ca-DTPA [30 mmol/kg]) administered ip at 1 h, 5 h (A), 16 h,more » 24 h (B), 3 d, or 7 d (C) post-contamination; mice euthanized 7 days after treatment. Data expressed as percent of injected 238Pu dose (% ID, mean ± SD) for each five-mouse group. Groups with significantly lower retention than for control mice are indicated by * or ** (p < 0.05 or p < 0.01, 1-way ANOVAwith post hoc Dunnett's multiple comparison test), while groups with significantly lower retention than for Ca-DTPA-treated mice are indicated by # or ## (p < 0.05 or p < 0.01, 1-way ANOVA with post hoc Tukey's HSD multiple comparison test).« less

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Works referencing / citing this record:

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
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  • Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; Abergel, Rebecca J.
  • Dalton Transactions, Vol. 48, Issue 23
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Toxic heavy metal – Pb, Cd, Sn – complexation by the octadentate hydroxypyridinonate ligand archetype 3,4,3-LI(1,2-HOPO)
journal, January 2018

  • Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; An, Dahlia D.
  • New Journal of Chemistry, Vol. 42, Issue 10
  • DOI: 10.1039/c7nj04559j

Toxic heavy metal – Pb, Cd, Sn – complexation by the octadentate hydroxypyridinonate ligand archetype 3,4,3-LI(1,2-HOPO)
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  • Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; An, Dahlia D.
  • New Journal of Chemistry, Vol. 42, Issue 10
  • DOI: 10.1039/c7nj04559j

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
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  • Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; Abergel, Rebecca J.
  • Dalton Transactions, Vol. 48, Issue 23
  • DOI: 10.1039/c9dt01031a

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  • Aupiais, J.; Younes, A.; Moisy, P.
  • New Journal of Chemistry, Vol. 41, Issue 19
  • DOI: 10.1039/c7nj02123b

Transforming lanthanide and actinide chemistry with nanoparticles
journal, January 2020

  • Pallares, Roger M.; Abergel, Rebecca J.
  • Nanoscale, Vol. 12, Issue 3
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    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.