Excretion of Pu-238 during Long-term Chelation Therapy by Repeated DTPA Inhalation

Grémy, Olivier; Blanchin, N.; Miccoli, Laurent

doi:10.1097/hp.0000000000001584

Cited by 3 publications

(13 citation statements)

References 25 publications

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“…Describing the dataset with a single solubility parameter indicated an insoluble material, in contrast to the determination of Grémy et al (10,11) that the material was soluble based on interviews with the worker. In this work, the best fit was obtained assuming an insoluble material, with an s p value of 7 3 10 À4 (Table 3).…”

Section: Materials Solubility Intake Estimation and Modeling Of Bioas...mentioning

confidence: 90%

“…The inhalation incident, along with a full description of the chelation treatment protocol have been described elsewhere ( 10 , 11 ). Briefly, the plutonium intake was detected after a routine fecal bioassay analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Previous papers describing this case (10,11) posited that the long-term efficacy of treatment and bioassay data could be best explained by intracellular chelation of plutonium, particularly in the liver. The objective of this paper was to model the bioassay data collected after the plutonium intake, including the measurements which were affected by chelation therapy, using a recently developed (9) and validated (1) chelation model by Dumit et al This model incorporates intracellular chelation in the skeleton and liver.…”

Section: Introductionmentioning

confidence: 92%

“…Previous works by Grémy et al (10,11,33,34) and Dumit et al (1,9,28,29) have shown and discussed in more details regarding the ability of Ca-DTPA to chelate intracellular plutonium in the liver and skeleton. The present work supports these past studies.…”

Section: Intracellular Chelationmentioning

confidence: 99%

“…The present work aimed to interpret the bioassay data of a male worker involved in a plutonium-238 inhalation incident and treated with DTPA, as the calcium chelate (Ca-DTPA), at the French Alternative Energies and Atomic Energy Commission (CEA), France. The case has been described in-depth elsewhere by Grémy et al ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA

Dumit,

Miller,

Grémy

et al. 2023

Radiation Research

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This work describes an analysis, using a previously established chelation model, of the bioassay data collected from a worker who received delayed chelation therapy following a plutonium-238 inhalation. The details of the case have already been described in two publications. The individual was treated with Ca-DTPA via multiple intravenous injections and then nebulizations beginning several months after the intake and continuing for four years. The exact date and circumstances of the intake are unknown. However, interviews with the worker suggested that the intake occurred via inhalation of a soluble plutonium compound. The worker provided daily urine and fecal bioassay samples throughout the chelation treatment protocol, including samples collected before, during, and after the administration of Ca-DTPA. Unlike the previous two publications presenting this case, the current analysis explicitly models the combined biokinetics of the plutonium-DTPA chelate. Using the previously established chelation model, it was possible to fit the data through optimizing only the intake (day and magnitude), solubility, and absorbed fraction of nebulized Ca-DTPA. This work supports the hypothesis that the efficacy of the delayed chelation treatment observed in this case results mainly from chelation of cell-internalized plutonium by Ca-DTPA (intracellular chelation). It also demonstrates the validity of the previously established chelation model. As the bioassay data were modified to ensure data anonymization, the calculation of the “true” committed effective dose was not possible. However, the treatment-induced dose inhibition (in percentage) was calculated.

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Section: Materials Solubility Intake Estimation and Modeling Of Bioas...mentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Intracellular Chelationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA

Dumit,

Miller,

Grémy

et al. 2023

Radiation Research

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Modelling DTPA therapy following Am contamination in rats

Kastl,

Grémy,

Lamart

et al. 2023

Radiat Environ Biophys

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A major challenge in modelling the decorporation of actinides (An), such as americium (Am), with DTPA (diethylenetriaminepentaacetic acid) is the fact that standard biokinetic models become inadequate for assessing radionuclide intake and estimating the resulting dose, as DTPA perturbs the regular biokinetics of the radionuclide. At present, most attempts existing in the literature are empirical and developed mainly for the interpretation of one or a limited number of specific incorporation cases. Recently, several approaches have been presented with the aim of developing a generic model, one of which reported the unperturbed biokinetics of plutonium (Pu), the chelation process and the behaviour of the chelated compound An–DTPA with a single model structure. The aim of the approach described in this present work is the development of a generic model that is able to describe the biokinetics of Am, DTPA and the chelate Am–DTPA simultaneously. Since accidental intakes in humans present many unknowns and large uncertainties, data from controlled studies in animals were used. In these studies, different amounts of DTPA were administered at different times after contamination with known quantities of Am. To account for the enhancement of faecal excretion and reduction in liver retention, DTPA is assumed to chelate Am not only in extracellular fluids, but also in hepatocytes. A good agreement was found between the predictions of the proposed model and the experimental results for urinary and faecal excretion and accumulation and retention in the liver. However, the decorporation from the skeletal compartment could not be reproduced satisfactorily under these simple assumptions.

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Actinide Decorporation: A Review on Chelation Chemistry and Nanocarriers for Pulmonary Administration

Lai

2022

Radiation Research

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Chelation is considered the best method for detoxification by promoting excretion of actinides (Am, Np, Pu, Th, U) from the human body after internal contamination. Chemical agents that possess carboxylic acid or hydroxypyridinonate groups play a vital role in actinide decorporation. In this review article, we provide considerable background details on the chelation chemistry of actinides with an aim to formulate better decorporation agents. Nanocarriers for pulmonary delivery represent an exciting prospect in the development of novel therapies for actinide decorporation that both reduce toxic side effects of the agent and improve its retention in the body. Recent studies have demonstrated the benefits of using a nebulizer or an inhaler to administer chelating agents for the decorporation of actinides. Effective chelation therapy with large groups of internally contaminated people can be a challenge unless both the agent and the nanocarrier are readily available from strategic national stockpiles for radiological or nuclear emergencies. Sunflower lecithin is particularly adept at alleviating the burden of administration when used to form liposomes as a nanocarrier for pulmonary delivery of diethylenetriamine-pentaacetic acid (DTPA) or hydroxypyridinone (HOPO). Better physiologically-based pharmacokinetic models must be developed for each agent in order to minimize the frequency of multiple doses that can overload the emergency response operations.

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Excretion of Pu-238 during Long-term Chelation Therapy by Repeated DTPA Inhalation

Cited by 3 publications

References 25 publications

Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA

Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA

Modelling DTPA therapy following Am contamination in rats

Actinide Decorporation: A Review on Chelation Chemistry and Nanocarriers for Pulmonary Administration

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