The development of molecular and nano actinide decorporation agents

Internal contamination of actinides has led to significant health hazards to the public and workers in the context of nuclear power plant accidents,uranium ore mining,and reprocessing of the used fuel.An effective sequestering agent that is able to remove accidentally incorporated actinides in vivo with low toxicity is always in urgent need.The molecular decorporation ligands have been the most widely researched agents for the past few decades,while preliminary studies of functionalized nanoparticles have shown their clear advantages in metal binding selectivity,toxicity,and oxidative stress alleviation.Herein,the state-of-the-art of those two types of decorporation agents is presented with special attention being paid on the correlation between the solution and solid-state chemistry of those agents with actinides and the corresponding decorporation efficacies.

Study of the decorporation efficacy and toxicity of tetradentate 3-hydroxy- 2-pyridinone ligands at the cellular level

Objective:A series of experiments were carried out to study the comparative decorporation efficacy and toxicity of three tetradentate hydroxypyridinone ligands(3LI-1-Cm-3,2-HOPO,5LIO-1-Cm-3,2-HOPO,and 7LIO-1-Cm-3,2-HOPO)with the variation of the linker length and the substituents.Methods:Three ligands were obtained from a 4-step synthesis via the amidation of HOPO unit and different backbones.Potentiometric titrations were carried out to evaluate the formation constants of their corresponding uranyl complexes.CCK-8 and colony formation assays were used to compare the cytotoxicity of the three ligands and uranyl using renal proximal tubular epithelial(NRK-52E)cells.In vitro uranium removal assays were performed to assess decorporation efficiencies of those ligands by co-incubating uranium and chelators with NRK-52E cells for 48 h.Results:Among the three ligands,5LIO-1-Cm-3,2-HOPO exhibits the highest uranyl affinity(logβ110?18.6(7))in comparison to the other two ligands(logβ110?14.9(2)for 3LI-1-Cm-3,2-HOPO and logβ110?16.7(1)for 7LIO-1-Cm-3,2-HOPO).The results of CCK-8 tests and colony formation assays further elucidate that 5LIO-1-Cm-3,2-HOPO and 7LIO-1-Cm-3,2-HOPO both show a similar level of cytotoxicity compared with ZnNa3-DTPA at relatively low ligand concentrations.In contrast,in the 3LI-1-Cm-3,2-HOPO treated group,the cell viability decreased markedly with the increase of the ligand concentrations,and the colony formation capability of NRK-52E cells was inhibited.Furthermore,the comparative decorporation efficacy of the three ligands was obtained from in vitro uranium removal assays,suggesting that these ligands could significantly inhibit the cellular uptake and prompt the cellular release of uranium from NRK-52E cells by the level of 81.9%,91.8%,and 87.1%,respectively.Conclusion:Our current results demonstrate that the linker/backbone species would significantly affect the decorporation efficacy and toxicity of the tetradentate 3-hydroxy-2-pyridinone ligands,which is informative for the future design and modification of novel decorporation ligands.

ssDNA functionalized nanodiamonds for uranium decorporation

The hunt for agents that are suitable for actinide decorporation to reduce the whole-body load of actinide in accidental internal exposure is the ever-lasting goal in radiation protection and medical treatment in nuclear emergency.All current decorporation agents can be categorized as two groups,one is the molecular ligands,and the other is the nanoparticles decorated with molecular ligands.Here in this work,functional nanodiamonds(fN Ds)with ss DNA(the endogenous biomacromolecule rich in phosphate groups)loaded on the NDs is reported,which poses good uranyl adsorption selectivity,high cellular uptake,fast excretion,and effective decorporation of uranyl from rat renal proximal tubular epithelial cells(NRK-52E).All those results corroborate that f NDs can potentially serve as a brand new family of chelators for actinide decorporation.

Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and,if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents(e.g., nitrites, dimethylaminophenol)or hydroxocobalamin(Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca(DTPA)or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca(DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

Preparing for a “dirty bomb” attack: The optimum mix of medical countermeasure resources

Background: In radiological emergencies with radionuclide incorporation, decorporation treatment is particularly effective if started early. Treating all people potentially contaminated("urgent treatment") may require large antidote stockpiles. An efficacious way to reduce antidote requirements is by using radioactivity screening equipment. We analyzed the suitability of such equipment for triage purposes and determined the most efficient mix of screening units and antidote daily doses.Methods: The committed effective doses corresponding to activities within the detection limits of monitoring portals and mobile whole-body counters were used to assess their usefulness as triage tools. To determine the optimal resource mix, we departed from a large-scale scenario(60,000 victims) and based on purchase prices of antidotes and screening equipment in Germany, we calculated efficiencies of different combinations of medical countermeasure resources by data envelopment analysis. Cost-effectiveness was expressed as the costs per life year saved and compared to risk reduction opportunities in other sectors of society as well as the values of a statistical life.Results: Monitoring portals are adequate instruments for a sensitive triage after cesium-137 exposure with a high screening throughput. For the detection of americium-241 whole-body counters with a lower daily screening capacity per unit are needed. Assuming that 1% of the potentially contaminated patients actually need decorporation treatment, an efficient resource mix includes 6 monitoring portals and 25 mobile whole-body counters. The optimum mix depends on price discounts and in particular the fraction of victims actually needing treatment. The costeffectiveness of preparedness for a "dirty bomb" attack is less than for common health care, but costs for a life year saved are less than for many risk-reduction interventions in the environmental sector.Conclusion: To achieve economic efficiency a high daily screening capacity is of major importance to substantially decrease the required amount of antidote doses. Among the determinants of the number of equipment units needed, the fraction of the potentially contaminated victims that actually needs treatment is the most difficult to assess. Judging cost-effectiveness of the preparedness for "dirty bomb" attacks is an issue of principle that must be dealt with by political leaders.

Medical management of victims contaminated with radionuclides after a “dirty bomb” attack

A wide spectrum of scenarios may lead to radiation incidents and the liberation of radioactive material. In the case of a terrorist attack by a "dirty bomb", there is a risk of mechanical and thermal trauma, external irradiation, superficial contamination and incorporation of radioactive material. The first treatment priority must be given to the care of trauma patients with life-threatening injuries, as the health effects of radiation occur with latency. Radionuclide incorporation will lead to a longer-lasting irradiation from inside the body, associated with a higher risk of stochastic radiation effects(e.g., occurrence of tumors) in the long run. It must be expected that victims with potentially incorporated radionuclides will far outnumber trauma patients. The elimination of radionuclides can be enhanced by the administration of decorporation agents such as(Ca) Diethylenetriaminepentaacetic acid(DTPA) or Prussian blue,reducing the radiological burden of the body. There is still no consensus whether decorporation treatment should be started immediately based only on a suspicion of radionuclide incorporation("urgent approach") or if the results of internal dosimetry confirming the necessity of a treatment should be awaited, accepting the delay caused by the measurements and computations("precautionary approach"). As the therapeutic effectiveness may be substantially decreased if treatment initiation is delayed only by several days, depending on the radionuclide, the physicochemical properties of the compounds involved and the route of absorption, we favor an "urgent approach" from a medical point of view. In doubt, it seems justified to treat victims by precaution, as the adverse effects of the medication seem minimal. However, in the case of a high number of victims, an "urgent treatment approach" may require a large number of daily doses of antidotes, and therefore, adequate investments in preparedness and antidote stockpiling are necessary.