Delivery of DTPA through Liposomes as a Good Strategy for Enhancing Plutonium Decorporation Regardless of Treatment Regimen.

In this study, we assessed the efficacy of unilamellar 110-nm liposomes encapsulating the chelating agent diethylenetriaminepentaacetic acid (DTPA) in plutonium-exposed rats. Rats were contaminated by intravenous administration of the soluble citrate form of plutonium. The comparative effects of liposomal and free DTPA at similar doses were examined in terms of limitation of alpha activity burden in rats receiving various treatment regimens. Liposomal DTPA given at 1 h after contamination more significantly prevented the accumulation of plutonium in tissues than did free DTPA. Also, when compared to free DTPA, liposome-entrapped DTPA was more efficient when given at late times for mobilization of deposited plutonium. In addition, repeated injections of liposomal DTPA further improved the removal of plutonium compared to single injection. Various possible mechanisms of action for DTPA delivered through liposomes are discussed. The advantage of liposomal DTPA over free DTPA was undoubtedly directly and indirectly due to the better cell penetration of DTPA when loaded within liposomes, mainly in the tissues of the mononuclear phagocytic system. The decorporation induced by liposomal DTPA may result first from intracellular chelation of plutonium deposited in soft tissues, predominantly in the liver. Afterwards, the slow release of free DTPA molecules from these same tissues may enable a sustained action of DTPA, probably mainly by extracellular chelation of plutonium available on bone surfaces. In conclusion, decorporation of plutonium can be significantly improved by liposomal encapsulation of DTPA regardless of the treatment regimen applied.

A rapid method for the sequential separation of polonium, plutonium, americium and uranium in drinking water.

A new sequential separation method for the determination of polonium and actinides (Pu, Am and U) in drinking water samples has been developed that can be used for emergency response or routine water analyses. For the first time, the application of TEVA chromatography column in the sequential separation of polonium and plutonium has been studied. This method utilizes a rapid Fe+3 co-precipitation step to remove matrix interferences, followed by plutonium oxidation state adjustment to Pu4+ and an incubation period of ~ 1 h at 50-60 °C to allow Po2+ to oxidize to Po4+. The polonium and plutonium were then separated on a TEVA column, while separation of americium from uranium was performed on a TRU column. After separation, polonium was micro-precipitated with copper sulfide (CuS), while actinides were micro co-precipitated using neodymium fluoride (NdF3) for counting by the alpha spectrometry. The method is simple, robust and can be performed quickly with excellent removal of interferences, high chemical recovery and very good alpha peak resolution. The efficiency and reliability of the procedures were tested by using spiked samples. The effect of several transition metals (Cu2+, Pb2+, Fe3+, Fe2+, and Ni2+) on the performance of this method were also assessed to evaluate the potential matrix effects. Studies indicate that presence of up to 25 mg of these cations in the samples had no adverse effect on the recovery or the resolution of polonium alpha peaks.

On the sequential separation and quantification of 237Np, 241Am, thorium, plutonium, and uranium isotopes in environmental and urine samples.

The implementation of the one-pass-through separation technique using two stacked chromatography columns of TEVA - TRU resins for the separation of 237Np, 241Am, thorium, plutonium and uranium from environmental and urine samples was investigated. The sequential separation technique proved to be successful and gave similar results to those obtained when using individual separations. The analysis time was considerably improved. The amount of chemical waste was also reduced by 50% and the use of HClO4 was avoided. The technique of ICP-MS was also investigated as a complementary technique to alpha-spectrometry.

Decorporation of Pu/Am Actinides by Chelation Therapy: New Arguments in Favor of an Intracellular Component of DTPA Action.

Diethylenetriaminepentaacetic acid (DTPA) is currently still the only known chelating drug that can be used for decorporation of internalized plutonium (Pu) and americium (Am). It is generally assumed that chelation occurs only in biological fluids, thus preventing Pu/Am deposition in target tissues. We postulate that actinide chelation may also occur inside cells by a mechanism called "intracellular chelation". To test this hypothesis, rats were given DTPA either prior to (termed "prophylactic" treatment) or belatedly after (termed "delayed" treatment) Pu/Am injection. DTPA decorporation efficacy was systematically tested for both plutonium and americium. Both prophylactic and delayed DTPA elicited marked decreases in liver Pu/Am. These results can be explained by chelation within subcellular compartments where DTPA efficacy increased as a function of a favorable intracellular DTPA-to-actinide molar ratio. The efficacy of intracellular chelation of liver actinides decreased with the delay of treatment. This is probably explained by progressive actinide binding to the high-affinity ligand ferritin followed by migration to lysosomes. Intracellular chelation was reduced as the gap between prophylactic treatment and contamination increased. This may be explained by the reduction of the intracellular DTPA pool, which declined exponentially with time. Skeletal Pu/Am was also reduced by prophylactic and delayed DTPA treatments. This decorporation of bone actinides may mainly result from extracellular chelation on bone surfaces. This work provides converging evidence for the involvement of an intracellular component of DTPA action in the decorporation process. These results may help to improve the interpretation of biological data from DTPA-treated contamination cases and could be useful to model DTPA therapy regimens.

A Novel Method for Tracer Concentration Plutonium(V) Solution Preparation.

Preparation of relatively pure low concentration Pu(V) solutions for environmental studies is nontrivial due to the complex redox chemistry of Pu. Ozone gas generated by an inexpensive unit designed for household-use was used to oxidize a 2 × 10(-8) M Pu(IV) solution to predominantly Pu(VI) with some Pu(V) present. Over several days, the Pu(VI) in the solution reduced to Pu(V) without further reducing to Pu(IV). The reduction from Pu(VI) to Pu(V) could be accelerated by raising the pH of the solution, which led to an immediate conversion without substantial conversion to Pu(IV). The aqueous Pu was found to be stable as predominately Pu(V) for greater than one month from pH 3-7; however, at circumneutral pH, a sizable fraction of Pu was lost from solution by either precipitation or sorption to the vial walls. This method provides a fast means of preparing Pu(V) solutions for tracer concentration studies without numerous extraction or cleanup steps.

Solution speciation of plutonium and Americium at an Australian legacy radioactive waste disposal site.

During the 1960s, radioactive waste containing small amounts of plutonium (Pu) and americium (Am) was disposed in shallow trenches at the Little Forest Burial Ground (LFBG), located near the southern suburbs of Sydney, Australia. Because of periodic saturation and overflowing of the former disposal trenches, Pu and Am have been transferred from the buried wastes into the surrounding surface soils. The presence of readily detected amounts of Pu and Am in the trench waters provides a unique opportunity to study their aqueous speciation under environmentally relevant conditions. This study aims to comprehensively investigate the chemical speciation of Pu and Am in the trench water by combining fluoride coprecipitation, solvent extraction, particle size fractionation, and thermochemical modeling. The predominant oxidation states of dissolved Pu and Am species were found to be Pu(IV) and Am(III), and large proportions of both actinides (Pu, 97.7%; Am, 86.8%) were associated with mobile colloids in the submicron size range. On the basis of this information, possible management options are assessed.

Comparison of sample preparation methods for reliable plutonium and neptunium urinalysis using automatic extraction chromatography.

This paper describes improvement and comparison of analytical methods for simultaneous determination of trace-level plutonium and neptunium in urine samples by inductively coupled plasma mass spectrometry (ICP-MS). Four sample pre-concentration techniques, including calcium phosphate, iron hydroxide and manganese dioxide co-precipitation and evaporation were compared and the applicability of different techniques was discussed in order to evaluate and establish the optimal method for in vivo radioassay program. The analytical results indicate that the various sample pre-concentration approaches afford dissimilar method performances and care should be taken for specific experimental parameters for improving chemical yields. The best analytical performances in terms of turnaround time (6h) and chemical yields for plutonium (88.7 ± 11.6%) and neptunium (94.2 ± 2.0%) were achieved by manganese dioxide co-precipitation. The need of drying ashing (≥ 7h) for calcium phosphate co-precipitation and long-term aging (5d) for iron hydroxide co-precipitation, respectively, rendered time-consuming analytical protocols. Despite the fact that evaporation is also somewhat time-consuming (1.5d), it endows urinalysis methods with better reliability and repeatability compared with co-precipitation techniques. In view of the applicability of different pre-concentration techniques proposed previously in the literature, the main challenge behind relevant method development is pointed to be the release of plutonium and neptunium associated with organic compounds in real urine assays. In this work, different protocols for decomposing organic matter in urine were investigated, of which potassium persulfate (K2S2O8) treatment provided the highest chemical yield of neptunium in the iron hydroxide co-precipitation step, yet, the occurrence of sulfur compounds in the processed sample deteriorated the analytical performance of the ensuing extraction chromatographic separation with chemical yields of ≤ 50%.

[Man-made radionuclides and their accumulation by plants of different taxonomic groups from the soils of the eastern ural radioactive trace].

Investigations of the spatial and vertical distribution of 90Sr, 137Cs and 239, 240Pu in the soils of the Eastern Ural Radioactive Trace (EURT) and accumulation of these radionuclides by plants were carried out in 2003-2011. Investigations showed that the spatial distribution of the radionuclides with increasing distances from the epicenter of the accident is satisfactorily approximated by the exponential function. During the post-accidental period the essential amount of radionuclides is located in the 15-20 cm root layer of the soil. Uptake by plants of 90Sr is determined, first of all, by the level of the soil contamination. For 137Cs, reliable differences in its accumulation ability between representatives of the higher plants and lower ones are remained in the whole gradient of contamination.

Bead injection extraction chromatography using high-capacity lab-on-valve as a front end to inductively coupled plasma mass spectrometry for urine radiobioassay.

A novel bead injection (BI) extraction chromatographic microflow system exploiting a high-capacity lab-on-valve (LOV) platform coupled with inductively coupled plasma mass spectrometric detection is developed for rapid and automated determination of plutonium in human urine. A column attached to the LOV processing unit is loaded online with a metered amount of disposable extraction chromatographic resin (up to 330 mg of TEVA (abbreviation for tetravalent actinides)) through programmable beads transport. Selective capture and purification of plutonium onto the resin beads is then performed by pressure driven flow after preliminary sample pretreatment. The analytical results demonstrate the large capacity of bead surfaces for uptake of Pu within the tailor-made LOV platform that fosters processing of large-sized biological samples, e.g., 1 L of human urine, along with good reproducibility for automatic column renewal (0.319 ± 0.004 g, n = 5). The chemical yields of plutonium were averagely better than 90% under the optimal experimental conditions, and the entire analytical procedure could be accomplished within a short time frame (<3 h) as compared to manual counterparts (1-2 days). Therefore, the developed system is well suited for expedient analysis of low-level plutonium in urine of exposed individuals as required in emergency situations.

Sorption coefficients and molecular mechanisms of Pu, U, Np, Am and Tc to Fe (hydr)oxides: a review.

Pu, U, Np, Am and Tc are among the major risk drivers at nuclear waste management facilities throughout the world. Furthermore, uranium mining and milling operations have generated an enormous legacy of radioactively contaminated soils and groundwater. The sorption process of radionulcides onto ubiquitous Fe (hydr)oxides (FHOs; hematite, magnetite, goethite and ferrihydrite) is one of the most vital geochemical processes controlling the transport and fate of radionuclides and nuclear wastes in the subsurface zones. Meanwhile, understanding molecular-level chemical speciation of radionuclides onto FHOs is crucial to model their behavior in subsurface environments, and to develop new technologies for nuclear waste treatment and long-term remediation strategies for contaminated soils and groundwater. This review article aims (1) to provide risk or performance assessment modelers with macroscopic distribution coefficient (K(d)) data of Pu, U, Np, Am and Tc onto FHOs under different conditions (pH, radionuclide concentration, solution ion strength, sorbent loading, partial pressure of CO(2) (P CO(2)), equilibrium time) pertinent to environmental and engineered systems, and (2) to provide a microscopic or molecular-level understanding of the chemical speciation and sorption processes of these radionuclides to FHOs.

Liquid-liquid extraction of Pu(IV), U(VI) and Am(III) using malonamide in room temperature ionic liquid as diluent.

The extraction behavior of U(VI), Pu(IV) and Am(III) from nitric acid medium by a solution of N,N-dimethyl-N,N-dioctyl-2-(2-hexyloxyethyl)malonamide (DMDOHEMA) in the room temperature ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (C(4)mimNTf(2)), was studied. The distribution ratio of these actinides in DMDOHEMA/C(4)mimNTf(2) was measured as a function of various parameters such as the concentration of nitric acid, DMDOHEMA, NTf(2)(-), alkyl chain length of ionic liquid. The extraction of actinides in the absence of DMDOHEMA was insignificant and the distribution ratio achieved in conjunction with C(4)mimNTf(2), was remarkable. The separation factor of U(VI) and Pu(IV) achieved with the use of DMDOHEMA, ionic liquid was compared with Am(III) and other fission products. The stoichiometry of the metal-solvate was determined to be 1:2 for U(VI) and Pu(IV) and 1:3 for Am(III).

Rapid determination of (237)Np and plutonium isotopes in urine by inductively-coupled plasma mass spectrometry and alpha spectrometry.

A new rapid separation method was developed for the measurement of plutonium and neptunium in urine samples by inductively-coupled plasma mass spectrometry (ICP-MS) and/or alpha spectrometry with enhanced uranium removal. This method allows separation and preconcentration of plutonium and neptunium in urine samples using stacked extraction chromatography cartridges and vacuum box flow rates to facilitate rapid separations. There is an increasing need to develop faster analytical methods for emergency response samples. There is also enormous benefit to having rapid bioassay methods in the event that a nuclear worker has an uptake (puncture wound, etc.) to assess the magnitude of the uptake and guide efforts to mitigate dose (e.g., tissue excision and chelation therapy). This new method focuses only on the rapid separation of plutonium and neptunium with enhanced removal of uranium. For ICP-MS, purified solutions must have low salt content and low concentration of uranium due to spectral interference of (238)U(1)H(+) on m/z 239. Uranium removal using this method is enhanced by loading plutonium and neptunium initially onto TEVA resin, then moving plutonium to DGA resin where additional purification from uranium is performed with a decontamination factor of almost 1×10(5). If UTEVA resin is added to the separation scheme, a decontamination factor of ~3 × 10(6) can be achieved.

Electrokinetic remediation of plutonium-contaminated nuclear site wastes: results from a pilot-scale on-site trial.

This paper examines the field-scale application of a novel low-energy electrokinetic technique for the remediation of plutonium-contaminated nuclear site soils, using soil wastes from the Atomic Weapons Establishment (AWE) Aldermaston site, Berkshire, UK as a test medium. Soils and sediments with varying composition, contaminated with Pu through historical site operations, were electrokinetically treated at laboratory-scale with and without various soil pre-conditioning agents. Results from these bench-scale trials were used to inform a larger on-site remediation trial, using an adapted containment pack with battery power supply. 2.4 m(3) (ca. 4t onnes) of Pu-contaminated soil was treated for 60 days at a power consumption of 33 kWh/m(3), and then destructively sampled. Radiochemical data indicate mobilisation of Pu in the treated soil, and migration (probably as a negatively charged Pu-citrate complex) towards the anodic compartment of the treatment cell. Soil in the cathodic zone of the treatment unit was remediated to a level below free-release disposal thresholds (1.7 Bq/g, or <0.4 Bq/g above background activities). The data show the potential of this method as a low-cost, on-site tool for remediation of radioactively contaminated soils and wastes which can be operated remotely on working sites, with minimal disruption to site infrastructure or operations.

Therapeutic whole lung lavage for inhaled plutonium oxide revisited.

Two reviews in the last 12 years have differed widely in their indications for the use of whole lung lavage (WLL) to remove plutonium from the lung, one recommending its use at relatively low radiation doses to prevent stochastic effects and the other recommending restricting its use to high doses to prevent deterministic effects only. Since the publication of these reviews significant data have accumulated demonstrating the increased safety of WLL, and there are additional data on stochastic and deterministic effects. We discuss deterministic and stochastic risks and the practical aspects of undertaking WLL. We recommend that each case be assessed individually.

Three plutonium chelation cases at Los Alamos National Laboratory.

Chelation treatments with dosages of 1 g of either Ca-DTPA (Trisodium calcium diethylenetriaminepentaacetate) or Zn-DTPA (Trisodium zinc diethylenetriaminepentaacetate) were undertaken at Los Alamos Occupational Medicine in three recent cases of wounds contaminated with metallic forms of Pu. All cases were finger punctures, and each chelation injection contained the same dosage of DTPA. One subject was treated only once, while the other two received multiple injections. Additional measurements of wound, urine, and excised tissues were taken for one of the cases. These additional measurements served to improve the estimate of the efficacy of the chelation treatment. The efficacy of the chelation treatments was compared for the three cases. Results were interpreted using models, and useful heuristics for estimating the intake amount and final committed doses were presented. In spite of significant differences in the treatments and in the estimated intake amounts and doses amongst the three cases, a difference of four orders of magnitude was observed between the highest excretion data point and the values observed at about 100 d for all cases. Differences between efficacies of Zn-DTPA and Ca-DTPA could not be observed in this study. An efficacy factor of about 50 was observed for a chelation treatment, which was administered at about 1.5 y after the incident, though the corresponding averted dose was very small (LA-UR 09-02934).

Functional sorbents for selective capture of plutonium, americium, uranium, and thorium in blood.

Self-assembled monolayer on mesoporous supports (SAMMS) are hybrid materials created from attachment of organic moieties onto very high surface area mesoporous silica. SAMMS with surface chemistries including three isomers of hydroxypyridinone, diphosphonic acid, acetamide phosphonic acid, glycinyl urea, and diethylenetriamine pentaacetate (DTPA) analog were evaluated for chelation of actinides ((239)Pu, (241)Am, uranium, thorium) from blood. Direct blood decorporation using sorbents does not have the toxicity or renal challenges associated with traditional chelation therapy and may have potential applications for critical exposure cases, reduction of nonspecific dose during actinide radiotherapy, and for sorbent hemoperfusion in renal insufficient patients, whose kidneys clear radionuclides at a very slow rate. Sorption affinity (K(d)), sorption rate, selectivity, and stability of SAMMS were measured in batch contact experiments. An isomer of hydroxypyridinone (3,4-HOPO) on SAMMS demonstrated the highest affinity for all four actinides from blood and plasma and greatly outperformed the DTPA analog on SAMMS and commercial resins. In batch contact, a fifty percent reduction of actinides in blood was achieved within minutes, and there was no evidence of protein fouling or material leaching in blood after 24 h. The engineered form of SAMMS (bead format) was further evaluated in a 100-fold scaled-down hemoperfusion device and showed no blood clotting after 2 h. A 0.2 g quantity of SAMMS could reduce 50 wt.% of 100 ppb uranium in 50 mL of plasma in 18 min and that of 500 dpm mL(-1) in 24 min. 3,4-HOPO-SAMMS has a long shelf-life in air and at room temperature for at least 8 y, indicating its feasibility for stockpiling in preparedness for an emergency. The excellent efficacy and stability of SAMMS materials in complex biological matrices suggest that SAMMS can also be used as orally administered drugs and for wound decontamination. By changing the organic groups of SAMMS, they can be used not only for actinides but also for other radionuclides. By using the mixture of these SAMMS materials, broad spectrum decorporation of radionuclides is very feasible.

Selectivity of 90Sr urine bioassay technique over 241Am, 238/239PU, 210PO, 137CS and 60CO.

The selectivity of a rapid (90)Sr bioassay technique over (241)Am, (238/239)Pu, (210)Po, (137)Cs and (60)Co has been investigated. Similar to (90)Sr, these radionuclides are likely to be used in radiological dispersive devices. The purpose of this study was to demonstrate the degree to which the (90)Sr bioassay technique is free from interference by these radionuclides if present in a urine matrix. The interfering radionuclides were removed (from (90)Sr) by their retention on an anion exchange column. While, recovery of the target radionuclide ((90)Sr) was found to be >or= 90 %, contributions from (241)Am, (242)Pu and (208)Po were found to be

Fractionation of plutonium in environmental and bio-shielding concrete samples using dynamic sequential extraction.

Fractionation of plutonium isotopes ((238)Pu, (239,240)Pu) in environmental samples (i.e. soil and sediment) and bio-shielding concrete from decommissioning of nuclear reactor were carried out by dynamic sequential extraction using an on-line sequential injection (SI) system combined with a specially designed extraction column. Plutonium in the fractions from the sequential extraction was separated by ion exchange chromatography and measured using alpha spectrometry. The analytical results show a higher mobility of plutonium in bio-shielding concrete, which means attention should be paid to the treatment and disposal of nuclear waste from decommissioning.

Separation techniques for quantification of radionuclides in environmental samples.

The reliable and quantitative measurement of radionuclides is important in order to determine environmental quality and radiation safety, and to monitor regulatory compliance. We examined soil samples from Podunajske Biskupice, near the city of Bratislava in the Slovak Republic, for the presence of several natural ((238)U, (232)Th, (40)K) and anthropogenic ((137)Cs, (90)Sr, (239)Pu, (240)Pu, (241)Am) radionuclides. The area is adjacent to a refinery and hazardous waste processing center, as well as the municipal incinerator plant, and so might possess an unusually high level of ecotoxic metals. We found that the levels of both naturally occurring and anthropogenic radionuclides fell within the expected ranges, indicating that these facilities pose no radiological threat to the local environment. During the course of our analysis, we modified existing techniques in order to allow us to handle the unusually large and complex samples that were needed to determine the levels of (239)Pu, (240)Pu, and (241)Am activity. We also rated three commercial techniques for the separation of 90Sr from aqueous solutions and found that two of them, AnaLig Sr-01 and Empore Extraction Disks, were suitable for the quantitative and reliable separation of (90)Sr, while the third, Sr-Spec Resin, was less so. The main criterion in evaluating these methods was the chemical recovery of (90)Sr, which was less than we had expected. We also considered speed of separation and additional steps needed to prepare the sample for separation.

Source-dependent and source-independent controls on plutonium oxidation state and colloid associations in groundwater.

Plutonium (Pu) was characterized for its isotopic composition, oxidation states, and association with colloids in groundwater samples near disposal basins in F-Area of the Savannah River Site and compared to similar samples collected six years earlier. Two sources of Pu were identified, the disposal basins, which contained a 24Pu/l39Pu isotopic signature consistent with weapons grade Pu, and 244Cm, a cocontaminant that is a progenitor radionuclide of 24Pu. 24Pu that originated primarily from 244Cm tended to be appreciably more oxidized (Pu(V/VI)), less associated with colloids (approximately 1 kDa - 0.2 microm), and more mobile than 239Pu, as suggested by our prior studies at this site. This is not evidence of isotope fractionation but rather "source-dependent" controls on 240Pu speciation which are processes that are not at equilibrium, i.e., processes that appear kinetically hindered. There were also "source-independent" controls on 239Pu speciation, which are those processes that follow thermodynamic equilibrium with their surroundings. For example, a groundwater pH increase in one well from 4.1 in 1998 to 6.1 in 2004 resulted in an order of magnitude decrease in groundwater 239Pu concentrations. Similarly, the fraction of 239Pu in the reduced Pu(III/IV) and colloidal forms increased systematically with decreases in redox condition in 2004 vs 1998. This research demonstrates the importance of source-dependent and source-independent controls on Pu speciation which would impact Pu mobility during changes in hydrological, chemical, or biological conditions on both seasonal and decadal time scales, and over short spatial scales. This implies more dynamic shifts in Pu speciation, colloids association, and transport in groundwater than commonly believed.