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

Journal Article · · Chemico-Biological Interactions
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  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
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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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
National Inst. of Health (NIH); SC-22.1 USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1458488
Alternate ID(s):
OSTI ID: 1397624
Journal Information:
Chemico-Biological Interactions, Journal Name: Chemico-Biological Interactions Journal Issue: C Vol. 267; ISSN 0009-2797
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (7)

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents journal March 2018
Simple measurement of actinides in urine using solid-state scintillation journal July 2019
Multiple Patients With Burn Injury Induced by a Chemical Explosion Managed by Physician-Staffed Helicopters journal January 2019
Structural and thermodynamic investigation of An IV LI(O)HOPO journal January 2017
Toxic heavy metal – Pb, Cd, Sn – complexation by the octadentate hydroxypyridinonate ligand archetype 3,4,3-LI(1,2-HOPO) journal January 2018
Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones journal January 2019
Transforming lanthanide and actinide chemistry with nanoparticles journal January 2020

Figures / Tables (5)

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61 RADIATION PROTECTION AND DOSIMETRY
Chelation therapy
Contamination
Medical countermeasure
Prophylaxis
Radionuclides