Action of DTPA on Hepatic Plutonium: III. Evidence for a Direct Chelation Mechanism for DTPA-Induced Excretion of Monomeric Plutonium into Rat Bile

Bhattacharyya, Maryka H.; Peterson, D.P.

doi:10.2307/3575119

Cited by 19 publications

(15 citation statements)

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“…Experiments have also shown that Ca-DTPA does not chelate plutonium significantly after the element’s deposition in organs, explaining the necessity of administering treatment as soon as possible post-contamination [10]. However, although the large molar percentage of DTPA administered parenterally can be accounted for in blood and extracellular fluid, a small fraction can reach intracellular spaces responsible for the liver decorporation efficacy, as demonstrated in rats and dogs [11, 12]. Additionally, DTPA’s side effects include the loss of essential metals such as zinc and magnesium from the body, further emphasizing the need for alternative decorporation therapy.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Therefore, the prolonged effect of DTPA on the biliary excretion of 59Fe in the present study may be attributable to a small portion of DTPA remaining in the liver after most of the DTPA has been cleared from the blood by the kidneys. 11,12) In Experiment II where the DTPA treatment was started 24 h after 59Fe injection, the systemic distribution and fecal excretion of 59Fe were essentially the same as those in Experiment I where the treatment were started 30 min postinjection. But the urinary excretion in delayed treatment (Experiment I) was 62% and 44% of that in prompt treatment (Experiment II) with H5-DTPA and Ca-DTPA, respectively.…”

Section: Discussionmentioning

confidence: 59%

Effects of H5-DTPA and Ca-DTPA on the removal of 59Fe from rats injected with 59Fe-iron dextran.

Sato¹,

Kubota²,

Takahashi³

et al. 1989

Jpn. J. Health Phys.

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Rats injected intravenously with the 59Fe-iron dextran were treated with two chelating agents, H5-DTPA and Ca-DTPA.The removal effects were compared between H5-DTPA and Ca-DTPA to estimate the usefulness of H5-DTPA for the chelating treatment in the accidental contamination with radioactive metal elements.H5-DTPA was administered by subcutaneous implantation and Ca-DTPA by intraperitoneal injection 30 min or 24 h after the injection of 59Fe-iron dextran.The tissue distribution of 59Fe was not largely different between the treatments with two chelating agents. The excretion of 59Fe into the feces was increased with both H5-and Ca-DTPA to about 7 times that of control. With respect to the fecal excretion, the effect of H5-DTPA was the same level as that of Ca-DTPA treated group. On the other hand, the urinary excretion was strongly increased by the H5-DTPA treatment and the effect was 3. 4 times that of Ca-DTPA treated rats.

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“…of Pu-citrate (data not shown). Because the excretion ratio of actinides in urine vs. faeces is far lower than that measured after Am-DTPA contamination, the faecal decorporation of americium involves intracellular liver compartments and excretion occurs via the bile as it has been shown previously for plutonium (Bhattacharyya and Peterson 1979). The decreased faecal excretion of americium in treated rats compared with controls is explained by two pathways of liver decorporation by DTPA, bile and blood, as it has been shown after specific liver contamination ).…”

Section: Decorporation Of Americium After Systemic Contamination Of Rmentioning

confidence: 69%

Structure of a Single Model to Describe Plutonium and Americium Decorporation by Dtpa Treatments

Fritsch¹,

Sérandour²,

Grémy³

et al. 2010

Health Physics

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The aim of this study is to propose a single modeling structure to describe both plutonium and americium decorporation by DTPA, which is based on hypotheses mostly validated by experimental data. Decorporation efficacy of extracellular retention depends on the concentration ratio of DTPA vs. actinides and varies in each compartment according to the amount of biological ligands and their affinity for actinides. By contrast, because the relatively long residence time of DTPA after its cell internalization and the stability of actinide-DTPA complexes, intracellular decorporation efficacy is mainly controlled by a DTPA/actinide ratio, which is specific to each retention compartment. Although the affinity of DTPA is much lower for americium than for plutonium, a larger decorporation of americium can be obtained, which is explained by different biological ligands and/or their affinity for the actinide. Altogether, these results show that the relative contribution of intra vs. extracellular decorporation varies depending on the actinide, the chemical form of radionuclides, the galenic formulation of DTPA, and the treatment schedule.

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Action of DTPA on Hepatic Plutonium: III. Evidence for a Direct Chelation Mechanism for DTPA-Induced Excretion of Monomeric Plutonium into Rat Bile

Cited by 19 publications

References 0 publications

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

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

Effects of H5-DTPA and Ca-DTPA on the removal of 59Fe from rats injected with 59Fe-iron dextran.

Structure of a Single Model to Describe Plutonium and Americium Decorporation by Dtpa Treatments

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