Chelation Treatment by Early Inhalation of Liquid Aerosol DTPA for Removing Plutonium after Rat Lung Contamination

Miccoli, Laurent; Ménétrier, Florence; Laroche, Pierre; Grémy, Olivier

doi:10.1667/rr15451.1

Cited by 15 publications

(10 citation statements)

References 21 publications

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“…In association with this drug, the use of DTPA, able to chelate the dissolved species generated by Asc action, should enhance cobalt urinary excretion. DTPA can be administered in rats by inhalation (Miccoli et al, 2019) and Asc either via oral or intraperitoneal route as it has been previously shown that those two administration modes decrease lung damage in rats (Fanucchi et al, 2012;Mohamed et al, 2019) . The viability of THP-1 cells exposed to ligands was evaluated by the resazurin assay.…”

Section: Discussionmentioning

confidence: 99%

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

Meeren

Devilliers

Coudert

et al. 2022

Toxicology in Vitro

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Section: Discussionmentioning

confidence: 99%

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

Meeren

Devilliers

Coudert

et al. 2022

Toxicology in Vitro

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“…A chronic treatment in the long term may be necessary too, depending on the particular case, but this consideration goes beyond the scope of the wound contamination experiments reported here. Recent results obtained in the laboratory after injection or inhalation of Pu provide indications that DTPA protocols need to be tailored for each patient and that DTPA inhalation is also a useful route of administration for decorporation therapy (Gremy et al 2017; Miccoli et al 2019).…”

Section: Discussionmentioning

confidence: 99%

DTPA Treatment of Wound Contamination in Rats with Americium: Evaluation of Urinary Profiles Using STATBIODIS Shows Importance of Prompt Administration

et al. 2021

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INTRODUCTION:In the nuclear industry wound contamination with americium is expected to increase with decommissioning and waste management. Treatment of workers with diethylenetriaminepentaacetic acid (DTPA) requires optimization to reduce internal contamination and radiation exposure. OBJECTIVES:To evaluate and compare different DTPA protocol efficacies after wound contamination of rats with americium. METHODS:Wound contamination was simulated in rats by depositing americium nitrate in an incision in the hind limb. Different routes, times and frequencies of DTPA administration were evaluated. Individual daily urinary americium excretion and tissue retention were analyzed using the statistical tool STATBIODIS. Urinary profiles, urinary enhancement factors and inhibition percentages of tissue retention were calculated. RESULTS:A single DTPA administration the day of contamination induced a rapid increase in americium urinary excretion that decreased exponentially over seven days indicating that the first DTPA administration should be delivered early as possible. DTPA treatment limited americium uptake in systemic tissues irrespective of the protocol. Liver and skeleton burdens were markedly reduced which would drive reduction of radiation dose. Local or intravenous injections were equally effective.Inherent difficulties in wound site activity measurements did not allow identification of a significant decorporating effect at the wound site. Repeated intravenous injections of DTPA also increased americium urinary excretion which supports the use of multiple DTPA administrations shortly after wound contamination. CONCLUSION:Results from these statistical analyses will contribute to a better understanding of americium behavior in the presence or absence of DTPA, and may aid optimization of treatment for workers.

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“…group; 15 µmol/kg) or nose-only exposed to an aerosol of DTPA solution ("DTPA local" group) diluted in NaCl 0.9% (deep lung deposit of 1.1 µmol/kg), by using an inhalation chamber associated with an Aeroneb ® lab micropump nebulizer (technology of a microperforated vibrating membrane; Tem Sega, Pessac, France). The exposure apparatus and DTPA dose determination with 111 In have been reported in detail elsewhere (Miccoli et al, 2019).…”

Section: Dtpa Treatment Regimensmentioning

confidence: 99%

Comparison of Local and Systemic DTPA Treatment Efficacy According to Actinide Physicochemical Properties Following Lung or Wound Contamination in the Rat

2021

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Purpose: In cases of occupational accidents in nuclear facilities or subsequent to terrorist activities, the most likely routes of internal contamination with alpha-particle emitting actinides, such as plutonium (Pu) and americium (Am), are by inhalation or following wounding. Following contamination, actinide transfer to the circulation and subsequent deposition in skeleton and liver depends primarily on the physicochemical nature of the compound. The treatment remit following internal contamination is to decrease actinide retention and in consequence potential health risks, both at the contamination site and in systemic retention organs as well as to promote elimination. The only approved drug for decorporation of Pu and Am is the metal chelator diethylenetriaminepentaacetic acid (DTPA). However, a limited efficacy of DTPA has been reported following contamination with insoluble actinides, irrespective of the contamination route. The objectives of this work are to evaluate the efficacy of prompt local and/or systemic DTPA treatment regimens following lung or wound contamination by actinides with differing solubility. The conclusions are drawn from retrospective analysis of experimental studies carried out over 10 years.Materials and Methods: Rat lungs or wounds were contaminated either with poorly soluble Mixed OXide (U, Pu O2) or more soluble forms of Pu (nitrate or citrate). DTPA treatment was administered promptly after contamination, locally to lungs by insufflation of a powder or inhalation of aerosolized solution or by injection directly into the wound site. Intravenous injections of DTPA were given either once or repeated in combination with the local treatment. Doses ranged from 1 to 30 µmol/kg. Animals were euthanized from day 7–21 and alpha activity levels were measured in urine, lungs, wound, bone and liver for determination of decorporation efficacy.Results: Different experiments confirmed that whatever the route of contamination, most of the activity is retained at the entry site after insoluble MOX contamination as compared with contamination with more soluble forms which results in very low activities reaching the systemic compartment and subsequent retention in bone and liver. Several DTPA treatment regimens were evaluated that had no significant effect on either lung or wound levels compared with untreated animals. In contrast, in all cases systemic retention (skeleton and liver) was reduced and urinary excretion were enhanced irrespective of the contamination route or DTPA treatment regimen.Conclusion: The present study demonstrates that despite limitation of retention in systemic organs, different DTPA protocols were ineffective in removing insoluble actinides deposited in lungs or wound site. For moderately soluble actinides, local or intravenous DTPA treatment reduced activity levels both at contamination and at systemic sites.

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Chelation Treatment by Early Inhalation of Liquid Aerosol DTPA for Removing Plutonium after Rat Lung Contamination

Cited by 15 publications

References 21 publications

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

DTPA Treatment of Wound Contamination in Rats with Americium: Evaluation of Urinary Profiles Using STATBIODIS Shows Importance of Prompt Administration

Comparison of Local and Systemic DTPA Treatment Efficacy According to Actinide Physicochemical Properties Following Lung or Wound Contamination in the Rat

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