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

doi:10.1016/j.cbi.2016.03.034

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 »« less

Authors:

An, Dahlia D. ^[1]; Kullgren, Birgitta ^[1]; Jarvis, Erin E. ^[1]; Abergel, Rebecca J. ^[1]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division

Publication Date:: 2016-03-31

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:: 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.

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                    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.

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                    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.

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@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},

  number       = C,

  volume       = 267,

  place        = {United States},

  year         = {2016},

  month        = {3}

}

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Journal Article:

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DOI: 10.1016/j.cbi.2016.03.034

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Cited by: 7 works

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Figures / Tables:

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 »

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Works referencing / citing this record:

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
journal, January 2019

Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; Abergel, Rebecca J.
Dalton Transactions, Vol. 48, Issue 23
DOI: 10.1039/c9dt01031a

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
journal, January 2019

Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; Abergel, Rebecca J.
Dalton Transactions, Vol. 48, Issue 23
DOI: 10.1039/c9dt01031a

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Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.

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Similar Records

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

Abstract

Citation Formats

Figures / Tables:

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones journal, January 2019

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones journal, January 2019

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
journal, January 2019

Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones
journal, January 2019