Validation of a system of models for plutonium decorporation therapy

Dumit, Sara; Avtandilashvili, Maia; McComish, Stacey L.; Strom, Daniel J.; Tabatadze, George; Tolmachev, Sergei Y.

doi:10.1007/s00411-018-00773-y

Cited by 17 publications

(12 citation statements)

References 18 publications

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“…Nevertheless, the activity level cleared in urine following DTPA administration diminished with therapy progression. This has already been observed in previously reported cases who received a prolonged chelation treatment regimen, regardless of when therapy was started and the radiocompound concerned [Am oxide, early treatment: [15]; Pu nitrate, early treatment [16]; Am oxide, early treatment: [7]; Pu nitrate, delayed treatment [17]; Am nitrate, delayed treatment: [4]; Pu nitrate, delayed DTPA treatment: [5], [6], [18]; Pu nitrate, delayed treatment: [8]].…”

Section: Dtpa-enhanced Elimination Of Plutonium Slowly Diminishes As supporting

confidence: 58%

Interpretation of Enhanced Fecal and Urinary Plutonium Excretions Under a 2-year Regular DTPA Treatment Started Months after Intake: A Case Report.

Grémy¹,

Blanchin²,

Miccoli³

2020

Preprint

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Background: Internal contamination with plutonium is a potential hazard for workers handling this alpha-emitting transuranic element. The only medical approach available for reducing potential health effects is to promote plutonium excretion by chelation therapy with diethylenetriaminepentaacetic acid (DTPA). Because of its poor distribution in plutonium retention tissues, DTPA should be initiated as early as possible after contamination to achieve maximum chelation when plutonium is still circulating. Treatment efficacy is usually evaluated by measuring the alpha activity in urine collected in the first 24 hours following DTPA administration as it is widely assumed that plutonium-DTPA complexes are very predominantly cleared within 24 hours.Case presentation: In a worker who had internalized plutonium-238 most likely through inhalation of a soluble compound, an extensive DTPA treatment regimen was initiated several months after contamination. Numerous radiotoxicological analyses were performed in both fecal and urinary specimens collected sometimes for three days after DTPA administration.Conclusions: Activity measurements showed the continued effectiveness of DTPA intravenous infusions in removing plutonium from tissues of retention even if the treatment regimen started several months after contamination. In the present case, the activity excreted through urine in the first 24 hours after a given DTPA administration was only about half of the total urinary plutonium excretion collected over three consecutive days. In addition, the careful study of the data revealed that DTPA-induced excretion of plutonium via fecal pathway significantly contributed to the overall decorporation. The intracellular chelation of plutonium which may be responsible for this enhanced excretion of activity in feces as well as for the delayed and sustained increased clearance of activity in urine. The authors would suggest that the occupational physicians offer to individuals who internalized plutonium compounds somewhat soluble to undergo a chronic DTPA treatment, especially when it is not initiated promptly after intake. Under this scenario, regular measurements of plutonium in successive urine and fecal collections after treatment should be required to get a better estimate of the therapeutic benefit. Also, intracellular chelation and fecal route should be taken into account for better interpretation of radiotoxicological data and modeling of plutonium kinetic under DTPA treatment.

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Section: Dtpa-enhanced Elimination Of Plutonium Slowly Diminishes As supporting

confidence: 58%

Interpretation of Enhanced Fecal and Urinary Plutonium Excretions Under a 2-year Regular DTPA Treatment Started Months after Intake: A Case Report.

Grémy¹,

Blanchin²,

Miccoli³

2020

Preprint

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“…Both these factors will limit transuranic deposition drastically in systemic target tissues, including the liver. In the present and other contamination cases [americium nitrate, delayed treatment ( Roedler et al 1989 ); plutonium nitrate, delayed DTPA treatment ( James et al 2007 ; Konzen et al 2016 ; Dumit et al 2019a )], individuals internalized moderately soluble forms of plutonium (nitrate) or americium (oxide), and the chelation treatment regimen was initiated belatedly. In these cases, because of the non-negligible fraction of the radiocompound quickly dissolved at the primary site of contamination and absorbed into the bloodstream, the amount of activity deposited in the liver, and hence in hepatocytes, should be sufficient enough to observe a treatment-induced increased fecal activity following DTPA treatment.…”

Section: Resultsmentioning

confidence: 81%

“…Thus, the long-term treatment regimen undergone by the present human case decorporated plutonium material even though it started late after plutonium internalization. Several previous studies of human cases have already reported an effectiveness of late DTPA therapies begun (or started again) several months or years after exposure to plutonium or americium [americium inhalation case ( Roedler et al 1989 ); USTUR plutonium inhalation case 0269 ( James et al 2007 ; Konzen et al 2016 ; Dumit et al 2019a ); USTUR americium inhalation case 0846 ( Breustedt et al 2019 ); and USTUR plutonium inhalation/wound case 0785 ( Dumit et al 2019b )]. In the present case, the late chelation treatments with 1-g DTPA did not appear more efficient than those with 0.5-g DTPA (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interpretation of Enhanced Fecal and Urinary Plutonium Excretion Data under a 2-y Regular DTPA Treatment Started Months after Intake

2021

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In a worker who had internalized plutonium, most likely through inhalation of a somewhat soluble compound, an extensive diethylenetriaminepentaacetate (DTPA) treatment regimen was initiated several months after contamination. Numerous radiotoxicological analyses were performed in both fecal and urinary specimens collected, sometimes for three consecutive days after DTPA administration. Activity measurements showed the continued effectiveness of DTPA intravenous infusions in removing plutonium from tissues of retention even if the treatment regimen started very belatedly after contamination. In the present case, the activity excreted through urine within the first 24-h after a DTPA infusion contributed only about half of that activity excreted within the first three days (i.e., the cumulative activity of the first three 24-h urine collections). In addition, the careful study of the data revealed that DTPA-induced excretion of plutonium via fecal pathway significantly contributed to the overall decorporation. The intracellular chelation of plutonium may be responsible for this enhanced excretion of activity in feces as well as for the delayed and sustained increased clearance of activity in urine. The authors would suggest that the occupational physicians offer to individuals who internalized moderately soluble or soluble plutonium compounds undergo a long-term DTPA treatment, especially when it is not initiated promptly after intake. Under this scenario, measurements of plutonium in successive urine and fecal collections after treatment should be required to get a better estimate of the therapeutic benefit. Also, intracellular chelation and fecal route should be taken into account for better interpretation of radiotoxicological data and modeling of plutonium kinetics under delayed DTPA treatment.

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“…In the present case, a chelation treatment regimen implemented a few years after Pu intake continued to be efficient for decorporating established Pu material. Long-term DTPA therapies have already been reported to be effective even when begun (or restarted) several months/years after Pu/Am internalization [Am inhalation case (Roedler et al 1989); USTUR Pu inhalation case 0269 (James et al 2007; Konzen et al 2016; Dumit et al 2019a); USTUR Am inhalation case 0846 (Breustedt et al 2019); USTUR Pu inhalation/wound case 0785 (Dumit et al 2019b); Pu inhalation case (Grémy et al 2021)]. However, these previously published papers concern DTPA-treated cases who received multiple administrations of DTPA by the conventional intravenous route, whereas the case described here received them by exposure to the aerosolized DTPA solution.…”

Section: Data Interpretationmentioning

confidence: 99%

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

2022

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An individual underwent an extensive diethylenetriaminepentaacetate (DTPA) chelation therapy that started several months after plutonium incorporation, most likely by inhalation of a soluble compound. After receiving multiple intravenous infusions of DTPA, the patient continued the treatment by pulmonary delivery of aerosolized DTPA. The purpose of the present work is to provide and discuss the bioassay data obtained during the DTPA aerosol therapy and compare them with those under the DTPA infusion therapy that have been largely interpreted elsewhere. As with DTPA given intravenously, each delayed DTPA inhalation increased the clearance of plutonium not only in urine but also in feces, thus demonstrating the ability to remove plutonium retained by extrapulmonary tissues. Also, the slow decline of increased plutonium urinary elimination together with enhanced fecal excretion are two features coherent with the contribution of intracellular chelation to overall decorporation. The therapeutic benefit of DTPA inhalation appeared lower than with DTPA infusion, most likely due to a lower amount of DTPA reaching the systemic compartments where plutonium chelation predominates. The results suggest that DTPA administration through aerosol could be an alternative to the invasive procedure using a needle, i.e., intravenous injection/infusion, when protracted decorporation therapy is needed following transuranic internalization. Indeed, the patient may be more inclined to undergo a chelation treatment for a longer period because taking DTPA by inhalation may make it less cumbersome and painful.

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Validation of a system of models for plutonium decorporation therapy

Cited by 17 publications

References 18 publications

Interpretation of Enhanced Fecal and Urinary Plutonium Excretions Under a 2-year Regular DTPA Treatment Started Months after Intake: A Case Report.

Interpretation of Enhanced Fecal and Urinary Plutonium Excretions Under a 2-year Regular DTPA Treatment Started Months after Intake: A Case Report.

Interpretation of Enhanced Fecal and Urinary Plutonium Excretion Data under a 2-y Regular DTPA Treatment Started Months after Intake

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

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