Incorporation of 241Am: Effectiveness of Late DTPA Chelation Therapy

Roedler, H.D.; Noßke, D.; Ohlenschläger, L; Schieferdecker, H.; Doerfel, H.; Renz, Kathleen J.

doi:10.1093/oxfordjournals.rpd.a080433

Cited by 12 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This shows that DTPA is able to increase plutonium excretion not only in urine but also in feces. Such an enhanced fecal elimination of activity in DTPA-treated contamination cases has been reported previously ( Norwood 1960 ; Roedler et al 1989 ; Piechowski et al 2003 ; James et al 2007 ). For example, a USTUR registrant who inhaled a liquid aerosol of plutonium nitrate received a DTPA treatment regimen that was started 2 y after the end of a previous intermittent chelation therapy with EDTA for 6 to 7 mo.…”

Section: Resultssupporting

confidence: 80%

“…Nevertheless, the activity level cleared in urine following DTPA administration diminished with therapy progression. This has already been observed in previously reported cases that received a prolonged chelation treatment regimen, regardless of when therapy was started and the radiocompound concerned [americium oxide, early treatment ( Fasiska et al 1971 ); plutonium nitrate, early treatment ( Jolly et al 1972 ); americium oxide, early treatment ( Breustedt et al 2019 ); plutonium nitrate, delayed treatment ( Jech et al 1972 ); americium nitrate, delayed treatment ( Roedler et al 1989 ); plutonium nitrate, delayed treatment ( James et al 2007 ; Konzen et al 2016 ; Dumit et al 2019a ); insoluble plutonium, delayed treatment ( Dumit et al 2019b )].…”

Section: Resultssupporting

confidence: 63%

“…Even though plutonium deposits established in bone tissue are usually considered to be retained tenaciously ( Chipperfield and Taylor 1970 , 1972 ) and hence not easily removable by DTPA ( Guilmette et al 2003 ) in humans, James et al observed an ability of multiple DTPA treatments to reduce skeletal plutonium level, predominantly from trabecular bone surfaces ( James et al 2007 ). With regard to the liver, a chelation of hepatic transuranic deposits in animals ( Bhattacharyya et al 1978 ; Grémy et al 2016 ) and humans ( Roedler et al 1989 ; James et al 2007 ) has been reported by several authors. More recently, Dumit et al (2019c and 2020b ) considered also that plutonium chelation can take place in systemic soft tissues including the liver and parts of skeleton.…”

Section: Resultsmentioning

confidence: 93%

“…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%

See 3 more Smart Citations

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

2021

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 80%

Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

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

2021

View full text Add to dashboard Cite

show abstract

“…Internal contamination with americium (or other transuranics) is rarely immediately life-threatening [National Council on Radiation Protection and Measurements, 2010], and i.v. DTPA treatment remains effective even when treatment is delayed by days following contamination [Roedler et al, 1989]. However, early treatment is much more beneficial, particularly when Ca-DTPA is administered in the first 24 h [Hameln Pharma GmbH, 2009].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a DTPA Prodrug, C2E5 as an Orally Bioavailable Radionuclide Decorporation Agent

Sadgrove

Leed

Shapariya

et al. 2012

Drug Development Research

View full text Add to dashboard Cite

Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV The efficacy of the prodrug C2E5, the pentaethyl ester of diethylenetriaminepentaacetic acid (DTPA), as an orally administered chelator of americium was evaluated in rats. C2E5 enhanced 241Am decorporation over vehicle‐only controls (187 μmol/kg, 14.8 ± 4.2% vs control, 7.1 ± 1.4% injected 241Am, P < 0.05) when administered 1 h after 241Am nitrate contamination by intramuscular (i.m.) injection. Reduction in liver burden was also achieved (375 μmol/kg, 13.1 ± 2.0% vs control, 17.3 ± 2.4% 241Am). Under these conditions, a single C2E5 dose did not match the efficacy of intravenous (i.v.) Ca‐DTPA (26.8 μmol/kg; decorporation 24.5 ± 3.5% and liver burden 10.2 ± 2.7% 241Am). Dividing the 375 μmol/kg C2E5 dose enhanced efficacy (4 × 94.5 μmol/kg C2E5; decorporation 19.7 ± 4.5% and liver burden 11.5 ± 2.8% 241 Am; P < 0.001, P < 0.05 vs control), approaching parity with i.v. Ca‐DTPA. When the contamination model was changed to i.v. or i.m. 241Am citrate injection, C2E5 (75 μmol/kg) enhanced decorporation and reduced liver burden. Higher doses of C2E5 (375 μmol/kg) were comparable with i.v. Ca‐DTPA (26.8 μmol/kg), with liver burdens at 3.2 ± 1.4% and 7.4 ± 2.7%, and decorporation of 43.5 ± 8.9% and 37.4 ± 3.9% i.m. 241Am citrate, respectively. The differences observed in oral C2E5 efficacy relative to i.v. Ca‐DTPA between contamination models may be related to the kinetics of the injected americium complex. C2E5 proved to be an effective decorporation agent for 241Am when orally administered and may be improved by optimized treatment strategies.

show abstract

Modelling DTPA therapy following Am contamination in rats

Kastl,

Grémy,

Lamart

et al. 2023

Radiat Environ Biophys

View full text Add to dashboard Cite

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.

show abstract

Incorporation of 241Am: Effectiveness of Late DTPA Chelation Therapy

Cited by 12 publications

References 0 publications

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

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

Evaluation of a DTPA Prodrug, C2E5 as an Orally Bioavailable Radionuclide Decorporation Agent

Modelling DTPA therapy following Am contamination in rats

Contact Info

Product

Resources

About