Chemical characterization of heavy actinides and light transactinides - Experimental achievements at JAEA.

The chemical characterization of the heaviest elements at the farthest reach of the periodic table (PT) and the classification of these elements in the PT are undoubtedly crucial and challenging subjects in chemical and physical sciences. The elucidation of the influence of relativistic effects on their outermost electronic configuration is also a critical and fascinating aspect. However, the heaviest elements with atomic numbers Z ≳ 100 must be produced at accelerators using nuclear reactions of heavy ions and target materials. Therefore, production rates for these elements are low, and their half-lives are as short as a few seconds to a few minutes; they are usually available in a quantity of only a few atoms at a time. Here, we review some highlighted studies on heavy actinide and light transactinide chemical characterization performed at the Japan Atomic Energy Agency tandem accelerator facility. We discuss briefly the prospects for future studies of the heaviest elements.

Efficient actinide sequestration with ionic liquid-based extraction chromatography resins containing Aza-crown ether functionalized diglycolamides.

Two new extraction chromatographic resins (ECRs) were prepared by impregnating two exotic diglycolamide (DGA) ligands (having three or four DGA moieties tethered to aza-crown ether scaffolds) dissolved in an ionic liquid onto an inert solid support. A room temperature ionic liquid (RTIL) was used for enhancing the performance of the ECRs. The ECR containing triaza-9-crown-3 functionalized with three DGA moieties (TAM-3-DGA), and tetraaza-12-crown-4 tethered with four DGA arms (TAM-4-DGA) were evaluated for the separation of Am3+ and Pu4+from nitric acid solutions. The resin capacity for Eu3+ was 9.52 mg/g and 7.24 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. Similarly, the resin capacity for Pu4+was 7.44 mg/g and 5.72 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. These maximum loading values corresponded to the formation of a 1:1 metal/ligand complex for the Eu3+ ion and a 1:2 metal/ligand complex for the Pu4+ ion. The sorption of Eu3+and Pu4+on the resins followed a chemisorption phenomenon on both resins. The sorbed Eu3+and Pu4+ions from the resin phase could be efficiently desorbed with complexing ligands such as guanidine carbonate/HEDTA and oxalic acid, respectively.

Impact of a Biological Chelator, Lanmodulin, on Minor Actinide Aqueous Speciation and Transport in the Environment.

Minor actinides are major contributors to the long-term radiotoxicity of nuclear fuels and other radioactive wastes. In this context, understanding their interactions with natural chelators and minerals is key to evaluating their transport behavior in the environment. The lanmodulin family of metalloproteins is produced by ubiquitous bacteria and Methylorubrum extorquens lanmodulin (LanM) was recently identified as one of nature's most selective chelators for trivalent f-elements. Herein, we investigated the behavior of neptunium, americium, and curium in the presence of LanM, carbonate ions, and common minerals (calcite, montmorillonite, quartz, and kaolinite). We show that LanM's aqueous complexes with Am(III) and Cm(III) remain stable in carbonate-bicarbonate solutions. Furthermore, the sorption of Am(III) to these minerals is strongly impacted by LanM, while Np(V) sorption is not. With calcite, even a submicromolar concentration of LanM leads to a significant reduction in the Am(III) distribution coefficient (Kd, from >104 to ∼102 mL/g at pH 8.5), rendering it even more mobile than Np(V). Thus, LanM-type chelators can potentially increase the mobility of trivalent actinides and lanthanide fission products under environmentally relevant conditions. Monitoring biological chelators, including metalloproteins, and their biogenerators should therefore be considered during the evaluation of radioactive waste repository sites and the risk assessment of contaminated sites.

The new QST bioassay laboratory in Chiba, Japan.

Japan's National Institutes for Quantum Science and Technology (QST) was designated as the core radiation emergency medical support center by the country's Nuclear Regulation Authority (NRA) in 2019. One of the main missions of the QST is to maintain and improve its dose assessment capability for radiation-exposed individuals. Toward the goal of effectively fulfilling this mission, a new facility-the Dose Assessment Building for Advanced Radiation Emergency Medicine-was constructed at the Chiba base of the QST in 2020. An integrated bioassay laboratory was installed in this facility for assessing subjects' internal doses, along with a new integrated in vivo counter. The bioassay capability of the new laboratory is currently expected to screen 5-10 persons simultaneously assuming internal contamination with actinides such as Pu, Am/Cm and U, although this is dependent on the specific contamination circumstances.

Rapid measurement of actinides in urine by mass and alpha spectrometric methods.

To provide timely information for prompting decision-making in emergency radiation therapy, we developed simple and rapid mass and alpha spectrometric methods for urinary bioassays to determine ultra-trace actinide isotopes. For the mass spectrometric method, after organic matter decomposition, LaF3/CaF2 co-precipitation and chromatographic purification using 2 ml of AG MP-1 M anion exchange resin, U and Pu isotopes were measured in a 20-ml urine sample by inductively coupled plasma-mass spectrometry. In the alpha spectrometric method, after organic matter decomposition, iron hydroxide co-precipitation and chromatographic purification using 2 ml of TEVA and 2 ml of DGA resin cartridges, Pu, U and Am/Cm isotopes were measured in a 500-ml urine sample by alpha spectrometry. These alpha and mass spectrometric methods were then applied for participation in the 2020 intercomparison organized by the Association for the PROmotion of Quality COntrol in RADiotoxicological Analysis (PROCORAD), France, for method validations.

α-Aminobisphosphonate Copolymers Based on Poly(ε-caprolactone)s and Poly(ethylene glycol): A New Opportunity for Actinide Complexation.

Original α-aminobisphosphonate-based copolymers were synthesized and successfully used for actinide complexation. For this purpose, poly(α-chloro-ε-caprolactone-co-ε-caprolactone)-b-poly(ethylene glycol)-b-poly(α-chloro-ε-caprolactone-co-ε-caprolactone) copolymers were first prepared by ring-opening copolymerization of ε-caprolactone (εCL) and α-chloro-ε-caprolactone using poly(ethylene glycol) (PEG) as a macro-initiator and tin(II) octanoate as a catalyst. The chloride functions were then converted to azide moieties by chemical modification, and finally α-aminobisphosphonate alkyne ligand (TzBP) was grafted using click chemistry, to afford well-defined poly(αTzBPεCL-co-εCL)-b-PEG-b-poly(αTzBPεCL-co-εCL) copolymers. Three copolymers, showing different α-aminobisphosphonate group ratios, were prepared (7, 18, and 38%), namely, CP8, CP9, and CP10, respectively. They were characterized by 1H and 31P NMR and size exclusion chromatography. Sorption properties of these copolymers were evaluated by isothermal titration calorimetry (ITC) with neodymium [Nd(III)] and cerium [Ce(III)] cations, used as surrogates of actinides, especially uranium and plutonium, respectively. ITC enabled the determination of the full thermodynamic profile and the calculation of the complete set of thermodynamic parameter (ΔH, TΔS, and ΔG), with the Ka constant and the n stoichiometry. The results showed that the number of cations sorbed by the functional copolymers logically increased with the number of bisphosphonate functions borne by the macromolecular chain, independently of the complexed cation. Additionally, CP9 and CP10 copolymers showed higher sorption capacities [21.4 and 34.0 mg·g-1 for Nd(III) and 9.6 and 14.3 mg·g-1 for Ce(III), respectively] than most of the systems previously described in the literature. CP9 also showed a highest binding constant (7000 M-1). These copolymers, based on non-toxic and biocompatible poly(ε-caprolactone) and PEG, are of great interest for external body decontamination of actinides as they combine high number of complexing groups, thus leading to great decontamination efficiency, and limited diffusion through the skin due to their high-molecular weight, thus avoiding additional possible internal contamination.

Europium(III) as luminescence probe for interactions of a sulfate-reducing microorganism with potentially toxic metals.

Microorganisms show a high affinity for trivalent actinides and lanthanides, which play an important role in the safe disposal of high-level radioactive waste as well as in the mining of various rare earth elements. The interaction of the lanthanide Eu(III) with the sulfate-reducing microorganism Desulfosporosinus hippei DSM 8344T, a representative of the genus Desulfosporosinus that naturally occurs in clay rock and bentonite, was investigated. Eu(III) is often used as a non-radioactive analogue for the trivalent actinides Pu(III), Am(III), and Cm(III), which contribute to a major part of the radiotoxicity of the nuclear waste. D. hippei DSM 8344T showed a weak interaction with Eu(III), most likely due to a complexation with lactate in artificial Opalinus Clay pore water. Hence, a low removal of the lanthanide from the supernatant was observed. Scanning transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy revealed a bioprecipitation of Eu(III) with phosphates potentially excreted from the cells. This demonstrates that the ongoing interaction mechanisms are more complex than a simple biosorption process. The bioprecipitation was also verified by luminescence spectroscopy, which showed that the formation of the Eu(III) phosphate compounds starts almost immediately after the addition of the cells. Moreover, chemical microscopy provided information on the local distribution of the different Eu(III) species in the formed cell aggregates. These results provide first insights into the interaction mechanisms of Eu(III) with sulfate-reducing bacteria and contribute to a comprehensive safety concept for a high-level radioactive waste repository, as well as to a better understanding of the fate of heavy metals (especially rare earth elements) in the environment.

Bispidine Chelators for Radiopharmaceutical Applications with Lanthanide, Actinide, and Main Group Metal Ions.

Octadentate and specifically nonadentate ligands with a bispidine scaffold (3,7-diazabicyclo[3.3.1]nonane) are known to be efficiently coordinated to a range of metal ions of interest in radiopharmaceutical chemistry and lead to exceedingly stable and inert complexes. Nonadentate bispidine L2 (with a tridentate bipyridine acetate appended to N3 and a picolinate at N7) has been shown before to be an ideal chelator for 111In3+, 177Lu3+, and 225Ac3+, nuclides of interest for diagnosis and therapy, and a proof-of-principle study with an SSTR2-specific octreotate has shown potential for theranostic applications. We now have extended these studies in two directions. First, we present ligand derivative L3, in which the bipyridine acetate is substituted with terpyridine, a softer donor for metal ions with a preference for more covalency. L3 did not fulfill the hopes because complexation is much less efficient. While for Bi3+ and Pb2+ the ligand is an excellent chelator with properties similar to those of L2, Lu3+ and La3+ show very slow and inefficient complexation with L3 in contrast to L2, and 225Ac3+ is not fully coordinated, even at an increased temperature (92% radiochemical yield at 80 °C, 60 min, [L3] = 10-4 M). These observations have led to a hypothesis for the complexation pathway that is in line with all of the experimental data and supported by a preliminary density functional theory analysis, which is important for the design of further optimized bispidine chelators. Second, the coordination chemistry of L2 has been extended to Bi3+, La3+, and Pb2+, including solid state and solution structural work, complex stabilities, radiolabeling, and radiostability studies. All complexes of this ligand (La3+, Ac3+, Lu3+, Bi3+, In3+, and Pb2+), including nuclides for targeted α therapy (TAT), single-photon emission computed tomography, and positron emission tomography, are formed efficiently under physiological conditions, i.e., suitable for the labeling of delicate biological vectors such as antibodies, and the complexes are very stable and inert. Importantly, for TAT with 225Ac, the daughter nuclides 213Bi and 209Pb also form stable complexes, and this is important for reducing damage to healthy tissue.

Rapid and reliable assaying of Tc-99 in sediment samples with novel MTPN polymeric resin.

The paper describes a new method for the rapid determination of Technetium (Tc) in sediment samples using solid-phase extraction chromatography (SPEC) with a novel methyl triphenyl phosphoniumnitrate (MTPN) resin. The effectiveness of the resin in selectively recovering Tc was evaluated in both batch and column mode and exploited for rapid analysis of 'Tc'. The procedure involves the acid digestion of samples, pre-concentration of fission products in supernatant and co-precipitation of actinides with Fe(OH)3, followed by selective recovery of Tc by SPEC using a column filled with MTPN resin. The recovered Tc was then radiometrically assayed using beta counting. The method was validated using IAEA certified reference materials and was found to provide reliable and reproducible results for the activity concentration of Tc-99 in sediment samples within 24 h.

Take a Swipe at Actinide Bioavailability: Application of a New In Vitro Method.

ABSTRACT: Filter swipe tests are used for routine analyses of actinides in nuclear industrial, research, and weapon facilities as well as following accidental release. Actinide physicochemical properties will determine in part bioavailability and internal contamination levels. The aim of this work was to develop and validate a new approach to predict actinide bioavailability recovered by filter swipe tests. As proof of concept and to simulate a routine or an accidental situation, filter swipes were obtained from a nuclear research facility glove box. A recently-developed biomimetic assay for prediction of actinide bioavailability was adapted for bioavailability measurements using material obtained from these filter swipes. In addition, the efficacy of the clinically-used chelator, diethylenetriamine pentaacetate (Ca-DTPA), to enhance transportability was determined. This report shows that it is possible to evaluate physicochemical properties and to predict bioavailability of filter swipe-associated actinides.

Organophosphorus Extractants: A Critical Choice for Actinides/Lanthanides Separation in Nuclear Fuel Cycle.

The separation of actinides from lanthanides in spent nuclear fuel reprocessing is a vital step of nuclear fuel cycle process. As one class of mature industrial extractants, the organophosphorus extractants have been widely used for the extraction and separation of actinides and lanthanides in spent fuel reprocessing due to their strong extraction ability and low-cost acquisition. In this concept, the application scope of tributyl phosphate (TBP), bis(2-ethylhexyl) phosphate (HDEHP), octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO), trialkyl phosphine oxide (TRPO), and purified Cyanex 301 (bis(2,4,4-trimethylpentyl) dithiophosphinic acid, HA301) are introduced, and their extraction mechanism, as well as structure-function relationships for separation of actinides over lanthanides are also discussed. Furthermore, the design criteria, extraction properties and mechanism of several typical newly developed organophosphorus extractants (CMPO-modified calixarene/pillarene, phenanthroline-derived organophosphorus extractants, and phosphate-modified carborane) based on pre-organized skeletons are briefly reviewed. Finally, the important role played by those organophosphorus extractants is emphasized and potential applications in separation of actinides over lanthanides in future advanced nuclear fuel cycle are identified.

Selective biosorption of lanthanides onto Galdieria sulphuraria.

The recovering of trivalent Lanthanides from aqueous solutions, by biosorption process onto Galdieria sulphuraria lifeless cells, was investigated. Potentiometry, UV-Vis, FTIR-ATR spectroscopy and SEM-EDS analysis were used. All the experiments were performed at 25 °C, in 0.5 M NaCl. Ln3+ biosorption is greater in the 5-6 pH range with values ranging from 80 µmol/g to 130 µmol/g (dry weight). The adsorbed Ln3+ ions can be recovered at higher acidity (pH<1) and the biosorbent can be reused. Specific molecular interactions between Ln3+ ions and the functional groups on G. sulphuraria surface were highlighted. Particularly, proteins are involved if Ln3+=Pr3+, Sm3+, Eu3+, Tb3+, Dy3+, Tm3+, while Ce3+, Ho3+, Er3+ form bonds with carbohydrates. Finally, both proteins and carbohydrates are involved if Gd3+ and Yb3+. A Surface Complexation approach, with a good graphical fitting to potentiometric experimental collected data, was used to describe the biosorption mechanism. This study could be of great applicative utility for removing of trivalent actinides, from waste aqueous solutions, by biosorption. As well known the lanthanides were used as model to simulate the chemical behaviour of actinides in the same oxidation state.

Chelating decorporation agents for internal contamination by actinides: Designs, mechanisms, and advances.

During the wide utilization of the actinides in medicine, energy, military, and other fields, internal contaminations can profoundly endanger human health and public security. Chelating decorporation agents are the most effective therapies to reduce internal contamination that includes radiological and chemical toxicities. This review introduces the structures of chelating decorporation agents including inorganic salts, polyaminocarboxylic acids, peptides, polyphosphonates, siderophores, calixarenes, polyethylenimines, and fullerenes, and highlights ongoing advances in their designs and mechanisms. However, there are still numerous challenges that block their applications including coordination properties, pharmacokinetic properties, oral bioavailability, limited timing of administration, and toxicity. Therefore, additional efforts are needed to push novel decorporation agents with high efficiency and low toxicity for the treatment of internal contamination by actinides.

Estimating the Gibbs Hydration Energies of Actinium and Trans-Plutonium Actinides.

The use of actinides for medical, scientific and technological purposes has gained momentum in the recent years. This creates a need to understand their interactions with biomolecules, both at the interface and as they become complexed. Calculation of the Gibbs binding energies of the ions to biomolecules, i. e., the Gibbs energy change associated with a transfer of an ion from the water phase to its binding site, could help to understand the actinides' toxicities and to design agents that bind them with high affinities. To this end, there is a need to obtain accurate reference values for actinide hydration, that for most actinides are not available from experiment. In this study, a set of ionic radii is developed that enables future calculations of binding energies for Pu3+ and five actinides with renewed scientific and technological interest: Ac3+ , Am3+ , Cm3+ , Bk3+ and Cf3+ . Reference hydration energies were calculated using quantum chemistry and ion solvation theory and agree well for all ions except Ac3+ , where ion solvation theory seems to underestimate the magnitude of the Gibbs hydration energy. The set of radii and reference energies that are presented here provide means to calculate binding energies for actinides and biomolecules.

Folding Dynamics of 3,4,3-LI(1,2-HOPO) in Its Free and Bound State with U4+ Implicated by MD Simulations.

The octadentate hydroxypyridonate ligand 3,4,3-LI(1,2-HOPO) (t-HOPO) shows strong binding affinity with actinide cations and is considered as a promising decorporation agent used to eliminate in vivo actinides, while its dynamics in its unbound and bound states in the condensed phase remain unclear. In this work, by means of MD simulations, the folding dynamics of intact t-HOPO in its neutral (t-HOPO0) and in its deprotonated state (t-HOPO4-) were studied. The results indicated that the deprotonation of t-HOPO in the aqueous phase significantly narrowed the accessible conformational space under the simulated conditions, and it was prepared in a conformation that could conveniently clamp the cations. The simulation of UIV-t-HOPO showed that the tetravalent uranium ion was deca-coordinated with eight ligating O atoms from the t-HOPO4- ligand, and two from aqua ligands. The strong electrostatic interaction between the U4+ ion and t-HOPO4- further diminished the flexibility of t-HOPO4- and confined it in a limited conformational space. The strong interaction between the U4+ ion and t-HOPO4- was also implicated in the shortened residence time of water molecules.

High-Throughput Determination of Ultratrace Actinides in Urine by In-Line Extraction Chromatography Combined with Quadrupole Inductively Coupled Plasma Mass Spectrometry (EC-ICP-MS).

Determining actinides in urine is vital for occupational exposure monitoring and radiological emergency response because of the toxicity and radiological dose effects of actinides on human health. Traditional radiochemistry analytical methods used to determine actinide concentrations in urine are time-consuming (sample analysis takes several days) and are hindered by a variety of technical and instrumentation-related obstacles. A high-throughput, fully automated, precise, and accurate in-line method was developed for determining five actinides (241Am, 239Pu, 237Np, 232Th, and 238U) at ng/L levels in urine using extraction chromatography combined with quadrupole inductively coupled plasma mass spectrometry (EC-ICP-MS). In this method, the five actinides were successfully separated with the required sensitivity, peak shape, and resolution using a simplified single Eichrom TRU column with a Dionex ICS-5000 system. The separated actinides were subsequently injected into an in-line PerkinElmer (PE) NexION 300D ICP-MS for quantitative determination. The sample-to-sample run time was 23 min for automatic chemical separation and quantification using only 0.5 mL of urine. The limits of detection (LOD) obtained using this method were 0.015, 0.022, 0.039, 4.5, and 2.4 ng/L for 241Am, 239Pu, 237Np, 232Th, and 238U, respectively. The method routinely had a chemical yield of >84% as well as a linearity (R2) coefficient of ≥0.999 for the calibrators. The method proved to be rapid, reliable, and effective for actinide quantification in urine and therefore is appropriate for radiological emergency response incidents.

Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands.

Speciation of actinides, and more particularly bioligand-binding ability, influences in vivo behavior. Understanding these interactions is essential for estimation of radiological dose and improvement of decorporation strategies for accidentally contaminated victims. Because the handling of actinides imposes overwhelming difficulties, in vitro assays carried out in physiological conditions are lacking and data regarding such interactions are scarce. In this study, we used a bi-compartmental and dynamic assay, providing physiological conditions (presence of inorganic ions, pH, temperature) to explore interactions between the actinides plutonium (Pu) and americium (Am) and endogenous (proteins transferrin and ferritin) or exogenous ligands (the chelating agent diethylenetriaminpentaacetic acid, DTPA). In this assay, an agarose gel represents the retention compartment of actinides and a dynamic fluid phase, the transfer compartment. The proportion of actinides transferred from static to dynamic phase reflects interactions between Pu/Am and various ligands. The results show differences in the formation of actinide-protein or actinide-DTPA complexes in physiologically relevant media depending on which ligand is present and where. We observed differential behavior for Pu and Am similar to in vivo studies. Thus, our assay may be used to determine the ability of various actinides to interact with specific proteins or with drug candidates for decorporation in complex physiologically relevant environments.

Speciation and spatial distribution of Eu(III) in fungal mycelium.

Europium, as an easy-to-study analog of the trivalent actinides, is of particular importance for studying the behavior of lanthanides and actinides in the environment. Since different soil organisms can influence the migration behavior of these elements, a detailed knowledge of these interaction mechanisms is important. The aim of this study was to investigate the interaction of mycelia of selected wood-inhabiting (S. commune, P. ostreatus, L. tigrinus) and soil-inhabiting fungi (L. naucinus) with Eu(III). In addition to determining the Eu(III) complexes in the sorption solution, the formed Eu(III) fungal species were characterized using scanning transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy, chemical microscopy in combination with the time-resolved laser-induced fluorescence spectroscopy. Our data show that S. commune exhibited significantly higher Eu(III) binding capacity in comparison to the other fungi. Depending on fungal strain, the metal was immobilized on the cell surface, in the cell membranes, and within the membranes of various organelles, or in the cytoplasm in some cases. During the bioassociation process two different Eu(III) fungal species were formed in all investigated fungal strain. The phosphate groups of organic ligands were identified as being important functional groups to bind Eu(III) and thus immobilize the metal in the fungal matrix. The information obtained contributes to a better understanding of the role of fungi in migration, removal or retention mechanisms of rare earth elements and trivalent actinides in the environment.

Actinide Decorporation: A Review on Chelation Chemistry and Nanocarriers for Pulmonary Administration.

Chelation is considered the best method for detoxification by promoting excretion of actinides (Am, Np, Pu, Th, U) from the human body after internal contamination. Chemical agents that possess carboxylic acid or hydroxypyridinonate groups play a vital role in actinide decorporation. In this review article, we provide considerable background details on the chelation chemistry of actinides with an aim to formulate better decorporation agents. Nanocarriers for pulmonary delivery represent an exciting prospect in the development of novel therapies for actinide decorporation that both reduce toxic side effects of the agent and improve its retention in the body. Recent studies have demonstrated the benefits of using a nebulizer or an inhaler to administer chelating agents for the decorporation of actinides. Effective chelation therapy with large groups of internally contaminated people can be a challenge unless both the agent and the nanocarrier are readily available from strategic national stockpiles for radiological or nuclear emergencies. Sunflower lecithin is particularly adept at alleviating the burden of administration when used to form liposomes as a nanocarrier for pulmonary delivery of diethylenetriamine-pentaacetic acid (DTPA) or hydroxypyridinone (HOPO). Better physiologically-based pharmacokinetic models must be developed for each agent in order to minimize the frequency of multiple doses that can overload the emergency response operations.

In Vitro and In Vivo Evaluation of DTPA-HPMA Copolymers as Potential Decorporating Agents for Prophylactic Therapy of Actinide Contamination.

The release of actinides into the environment represents a significant potential public health concern. Chelation therapy utilizing diethylenetriamine pentaacetate (DTPA) is a U.S. Food and Drug Administration (FDA)-approved therapy capable of mitigating the deposition of some absorbed actinides in the body. However, the pharmacokinetic profile of DTPA is not ideal for prophylactic applications. In this study, we examine the incorporation of DTPA into a HPMA copolymer (P-DTPA) to investigate if the enhanced blood circulation time can offer superior prophylactic protection and of improving in vivo radiometal decorporation. Utilizing lutetium-177 (177Lu) as an actinide model, the performance of P-DTPA and DTPA (control) were evaluated using selectivity studies in the presence of competing biological metals, chelation and stability assays in human serum and cytotoxicity studies using human umbilical vein endothelial cells (HUVEC). The in vivo decorporation efficiency of P-DTPA relative to DTPA and untreated controls was also evaluated over two weeks in CF-1 mice. In the experimental groups, the mice were prophylactically treated with P-DTPA or DTPA (30 µmol/kg) 6 or 24 h prior to 177LuCl3 administration. The in vitro results reveal that P-DTPA gives efficient complexation yields relative to DTPA with a tolerable cytotoxicity profile and good serum stability. The in vivo decorporation studies demonstrated enhanced total excretion of the 177Lu using P-DTPA compared to DTPA in both the 6 and 24 h prophylactic treatment study arms. This enhanced decorporation effect is certainly attributable to the expected prolonged biological half-life of DTPA when grafted to the HPMA polymer.