Recent Developments in the Decorporation of Plutonium, Americium and Thorium

Stradling, G.N.; Hodgson, S.; Pearce, M.J.

doi:10.1093/oxfordjournals.rpd.a032446

Cited by 14 publications

(21 citation statements)

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“…Rats given 241 Am, 238 Pu, or 239 Pu by injection as citrates or inhalation as nitrates, were given ZnNa 3 -DTPA in drinking water (l mmol L Ϫ1 , delivering Ն100 mol kg Ϫ1 d Ϫ1 per rat) for 2 to 10 weeks. Actinide retention in the lungs, liver, and bone was reduced about as much as with twice weekly injections of 30 mol kg Ϫ1 (Taylor and Volf 1980;Stradling et al 1993aStradling et al , 1998.…”

Section: Ethylenediaminetetraacetic Acid (H 4 -Edta)mentioning

confidence: 94%

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Durbin¹

2008

Health Physics

106

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All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage.

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Section: Ethylenediaminetetraacetic Acid (H 4 -Edta)mentioning

confidence: 94%

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Durbin¹

2008

Health Physics

106

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“…In in vivo studies designed to evaluate the actinide decorporation efficacy of experimental ligands, both hydroxypyridinonate ligands have been shown to significantly reduce the U and Th body burdens of contaminated animals after parenteral or oral treatments [2,10,32]. While a single parenteral treatment of contaminated rodents with DTPA can result in a reduction of U body content of up to 19%, as compared to untreated control animals, similar treatments with 5-LIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO) reduce the U body burden by 40 and 43%, respectively.…”

Section: From Solution Thermodynamics To In Vivo Decorporation Efficacymentioning

confidence: 99%

“…While a single parenteral treatment of contaminated rodents with DTPA can result in a reduction of U body content of up to 19%, as compared to untreated control animals, similar treatments with 5-LIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO) reduce the U body burden by 40 and 43%, respectively. The differences in effectiveness between DTPA and 3,4,3-LI(1,2-HOPO) were even more striking in Th decorporation studies [10]: in experiments where DTPA was determined to decrease the Th body content by 30%, the equivalent use of 3,4,3-LI(1,2-HOPO) resulted in up to 80% decreases. In detailed analyses of the various body compartments with residual radionuclides, the largest burden reductions were seen in the liver and kidneys, indicating that the hydroxypyridinonate ligands may successfully compete with endogenous metalbinding entities.…”

Section: From Solution Thermodynamics To In Vivo Decorporation Efficacymentioning

confidence: 99%

“…In addition, they both have displayed markedly higher potency than the commonly used actinide decorporation Brought to you by | University of Iowa Libraries Authenticated Download Date | 5/31/15 1:58 PM agent diethylenetriamine-pentaacetic acid (DTPA, Fig. 1) in decorporating a wide range of metal ions, including Th(IV), U(VI), Np(V), Pu(IV), and Am(III) [2,[8][9][10]. In the work presented here, the solution thermodynamic properties of UO 2 (VI) and Th(IV) complexes formed with 5-LIO(Me-3,2-HOPO) and 3,4,3-LI(1,2-HOPO) were probed and characterized by spectrophotometric titration methods.…”

Section: Introductionmentioning

confidence: 99%

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Solution thermodynamic evaluation of hydroxypyridinonate chelators 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) for UO₂(VI) and Th(IV) decorporation

Sturzbecher-Hoehne¹,

Deblonde²,

Abergel³

2013

Radiochimica Acta

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Spectrophotometric titration / Actinide decorporation / Hydroxypyridinonate ligands / UO 2 complexes / Th complexes Summary. Solution thermodynamic studies were performed to characterize the coordination of U(VI) and Th(IV) by the multidentate hydroxypyridinonate chelating agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Species distribution and conditional stability pM profiles were calculated based on the determined formation constants, showing that both ligands form extremely stable uranyl and thorium complexes in solution. At physiological pH, the formation of 1 : 1 ligand : uranyl complexes is favored for both ligands, while a 2 : 1 ligand : thorium complex is predominant with the tetradentate 5-LIO(Me-3,2-HOPO). Comparisons with functionally similar bidentate ligands as well as with the common actinide chelator diethylenetriamine pentaacetic acid emphasized the superior affinity for U(VI) and Th(IV) of both experimental compounds over a wide pH range. These analytical results corroborate the in vivo chelation efficacy of 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) and validate their selection for further development as therapeutic actinide decorporation agents.

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“…Siderophores and other naturally occurring ligands may therefore affect actinide mobility in waste repositories and the environment and may also be used to treat radioactive waste prior to storage or to decontaminate soils and waters (15,24,42,56). Siderophores and siderophore analogues have also been investigated for possible medical use in the decorporation of actinides from the body (25,48,49), while simple hydroxamates may have uses in the reprocessing of nuclear fuel (31,32,51,52).…”

mentioning

confidence: 99%

Development and Application of an Assay for Uranyl Complexation by Fungal Metabolites, Including Siderophores

Renshaw¹,

Halliday

Robson

et al. 2003

Appl Environ Microbiol

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An assay to detect UO 2 2؉ complexation was developed based on the chrome azurol S (CAS) assay for siderophores (B. Schwyn and J. B. Neilands, Anal. Biochem. 160:47-56, 1987) and was used to investigate the ability of fungal metabolites to complex actinides. In this assay the discoloration of two dyed agars (one containing a CAS-Fe 3؉ dye and the other containing a CAS-UO 2 2؉ dye) caused by ligands was quantified. The assay was tested by using the siderophore desferrioxamine B (DFO), and the results showed that there was a regular, reproducible relationship between discoloration and the amount of siderophore added. The ratio of the discoloration on the CAS-UO 2 2؉ agar to the discoloration on the CAS-Fe 3؉ agar was independent of the amount of siderophore added. A total of 113 fungi and yeasts were isolated from three soil samples taken from the Peak District National Park. The fungi were screened for the production of UO 2 2؉ chelators by using the CAS-based assay and were also tested specifically for hydroxamate siderophore production by using the hydroxamate siderophore auxotroph Aureobacterium flavescens JG-9. This organism is highly sensitive to the presence of hydroxamate siderophores. However, the CAS-based assay was found to be less sensitive than the A. flavescens JG-9 assay. No significant difference between the results for each site for the two tests was found. Three isolates were selected for further study and were identified as two Pencillium species and a Mucor species. Our results show that the new assay can be effectively used to screen fungi for the production of UO 2 2؉ chelating ligands. We suggest that hydroxamate siderophores can be produced by mucoraceous fungi.

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Recent Developments in the Decorporation of Plutonium, Americium and Thorium

Cited by 14 publications

References 0 publications

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Solution thermodynamic evaluation of hydroxypyridinonate chelators 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) for UO₂(VI) and Th(IV) decorporation

Development and Application of an Assay for Uranyl Complexation by Fungal Metabolites, Including Siderophores

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Recent Developments in the Decorporation of Plutonium, Americium and Thorium

Cited by 14 publications

References 0 publications

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Lauriston S. Taylor Lecture: The Quest for Therapeutic Actinide Chelators

Solution thermodynamic evaluation of hydroxypyridinonate chelators 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) for UO2(VI) and Th(IV) decorporation

Development and Application of an Assay for Uranyl Complexation by Fungal Metabolites, Including Siderophores

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Product

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Solution thermodynamic evaluation of hydroxypyridinonate chelators 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) for UO₂(VI) and Th(IV) decorporation