Development of the Plutonium-DTPA Biokinetic Model

Konzen, Kevin; Brey, Richard R.

doi:10.1097/hp.0000000000000283

Cited by 18 publications

(7 citation statements)

References 38 publications

(53 reference statements)

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“…Finally, although the health risks associated with Pu internal contamination are certainly reduced by eliminating the contaminant, reduction of the organ content is not directly proportional to dose reduction. Within the last decade, much attention has been paid to the development of computational tools to evaluate the radiation dose in animal models based on decorporation experimental data [28, 29]. Future work will focus on extending and applying such biodosimetry tools to delineate the effect of hydroxypyridinonate ligands on radiation dose reduction.…”

Section: Discussionmentioning

confidence: 99%

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

Kullgren

Jarvis

et al. 2017

Chemico-Biological Interactions

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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 presented 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 first 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 hours before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.

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Section: Discussionmentioning

confidence: 99%

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

Kullgren

Jarvis

et al. 2017

Chemico-Biological Interactions

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“…Specific models need to be developed for this purpose. Some models are already available, such as those for DTPA bound to plutonium [59,60], but a generic model, which would describe the biokinetics of the radionuclides after therapy and could be used for accurate dose assessment, is still missing. One of the many problems for the understanding and modeling of DTPA decorporation therapy is the still unknown sites of chelation and the identification of the bio-ligands and other molecules competing for the DTPA or the radionuclide binding [61].…”

Section: (4) Models For Radiopharmaceuticalsmentioning

confidence: 99%

Internal Dosimetry: State of the Art and Research Needed

Paquet

2022

J Radiat Prot Res

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Internal dosimetry is a discipline which brings together a set of knowledge, tools and procedures for calculating the dose received after incorporation of radionuclides into the body. Several steps are necessary to calculate the committed effective dose (CED) for workers or members of the public. Each step uses the best available knowledge in the field of radionuclide biokinetics, energy deposition in organs and tissues, the efficiency of radiation to cause a stochastic effect, or in the contributions of individual organs and tissues to overall detriment from radiation. In all these fields, knowledge is abundant and supported by many works initiated several decades ago. That makes the CED a very robust quantity, representing exposure for reference persons in reference situation of exposure and to be used for optimization and assessment of compliance with dose limits. However, the CED suffers from certain limitations, accepted by the International Commission on Radiological Protection (ICRP) for reasons of simplification. Some of its limitations deserve to be overcome and the ICRP is continuously working on this. Beyond the efforts to make the CED an even more reliable and precise tool, there is an increasing demand for personalized dosimetry, particularly in the medical field. To respond to this demand, currently available tools in dosimetry can be adjusted. However, this would require coupling these efforts with a better assessment of the individual risk, which would then have to consider the physiology of the persons concerned but also their lifestyle and medical history. Dosimetry and risk assessment are closely linked and can only be developed in parallel. This paper presents the state of the art of internal dosimetry knowledge and the limitations to be overcome both to make the CED more precise and to develop other dosimetric quantities, which would make it possible to better approximate the individual dose.

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“…A considerable effort has been made to generate methods and biokinetic models for interpreting the urinary excretion of plutonium under the influence of DTPA [1][2][3][4][5][6][7][8][9]. The approaches have evolved from empirical [1,2] to mechanistic [3] and most recently leaning towards pharmacokinetic approaches associating biokinetic compartments from the latest accepted plutonium systemic models [10] with those having more influence on the enhancement of the urinary excretion [4,5,6,9]. In addition, work has been published with practical applications for estimating the influence of the excretion enhancement factor on internal dose estimates [7].…”

Section: Introductionmentioning

confidence: 99%