Cyrille Alliot

Astatine Standard Redox Potentials and Speciation in Acidic Medium

A combined experimental and theoretical approach is used to define astatine (At) speciation in acidic aqueous solution and to answer the two main questions raised from literature data: does At(0) exist in aqueous solution and what is the chemical form of At(+III), if it exists. The experimental approach considers that a given species is characterized by its distribution coefficient (D) experimentally determined in a biphasic system. The change in speciation arising from a change in experimental conditions is observed by a change in D value. The theoretical approach involves quasi-relativistic quantum chemistry calculations. The results show that At at the oxidation state 0 cannot exist in aqueous solution. The three oxidation states present in the range of water stability are At(-I), At(+I), and At(+III) and exist as At(-), At(+), and AtO(+), respectively, in the 1-2 pH range. The standard redox potentials of the At(+)/At(-) and AtO(+)/At(+) couples have been determined, the respective values being 0.36 +/- 0.01 and 0.74 +/- 0.01 V vs NHE.

Investigation of astatine(III) hydrolyzed species: experiments and relativistic calculations.

This work aims to resolve some controversies about astatine(III) hydroxide species present in oxidant aqueous solution. AtO(+) is the dominant species existing under oxidizing and acidic pH conditions. This is consistent with high-performance ion-exchange chromatography data showing the existence of one species holding one positive charge. A change in speciation occurs as the pH changes from 1 to 4, while remaining under oxidizing conditions. Dynamic experiments with ion-exchange resins evidence the existence of a neutral species witnessed by its elution in the void volume. Batch-experiments using a competition method show the exchange of one proton indicating the formation of the AtO(OH) species. The hydrolysis thermodynamic constant, extrapolated to zero ionic strength, was determined to be 10(-1.9). This value is supported by two-component relativistic quantum calculations and therefore allows disclosing unambiguously the structure of the formed species.

Effect of aqueous acetic, oxalic and carbonic acids on the adsorption of americium onto α-alumina

Summary The prediction of the migration for radionuclides in geologic media requires a quantitative knowledge of retardation phenomena. For this purpose, the sorption of Am(III) onto a model mineral — α-alumina — is studied here, including the effects of groundwater chemistry: pH and concentrations of small organic ligands (acetate, oxalate and carbonate anions). This work presents some experimental evidences for the synergic sorption mechanism of americium–ligand cationic complexes onto the alumina. As its anionic complexes were not sorbed, Am(III) cations were desorbed as a result of the formation of anionic complexes in the aqueous phase. By using the ion-exchange theory, and a corresponding restricted set of parameters — exchange capacities and thermodynamic equilibrium constants — the whole set of sorption experiments of Am(III) cationic species onto the α-alumina was modelled in various chemical conditions.

Extraction of astatine-211 in diisopropylether (DIPE)

Abstract The extraction mechanism of astatine-211 in diisopropylether (DIPE) is studied by analyzing the effect of the nature of the aqueous solution and organic solvent on the distribution coefficients characterizing the ratio of organic and aqueous concentration of astatine (D). On the one hand, at a given pH value, D was shown to be independant of the nature and concentration of the counter-ion present in the aqueous solution (Cl-, ClO4-, NO3-). On the other hand, the nature of the organic solvent had a strong effect. D increases as the polarity of the organic solvent increases. These experimental observations are explained by the solvation of astatine by the organic solvent. The back-extraction of astatine from the organic to the aqueous phase is efficient in basic conditions. This is explained by the formation of a hydrolyzed species of astatine presenting no affinity for DIPE. Hydrolysis constants of astatine are deduced from experimental data (logβ1=-3.0±0.1 and logβ2=-14.2±0.1).

Speciation of technetium(IV) in bicarbonate media.

The technetium isotope (99)Tc is a major fission product from nuclear reactors. Ultimately it is disposed of as radioactive waste since it has few applications outside of scientific research. Geochemical modeling of the dissolution of nuclear waste and of the solubility and speciation of the dissolved radionuclides in groundwater is an important part of the Performance Assessment for the safety of nuclear waste repositories. It relies on the availability of a critically assessed thermodynamic database. The potential of the Tc(VII)/Tc(IV) redox couple is measured here under various chemical conditions to verify the stoichiometries of Tc complexes and determine their stabilities: (i) -log(10)[H(+)] in the range 7.0-10.0, for 0.3, 0.6, and 0.7 M [CO(3)](total); (ii) [CO(3)](total) in the range 0.01-0.6 M at -log(10)[H(+)] approximately 8.6; and (iii) [Tc(VII)]/[Tc(IV] ratios of (6.02 10(-5) M)/(10(-6) M) and (6.02 10(-5) M)/(6.02 10(-5) M) at -log(10)[H(+)] = -9.1 and [CO(3)](total) = 1 M. Assuming that Tc(VII), TcO(4)(-) is the only species which exists under all the above chemical conditions, the potentiometric results can be interpreted by considering the presence of two hydroxide-carbonate monomeric complexes. The hydrolysis equilibrium between these two complexes is Tc(CO(3))(OH)(2) + H(2)O <--> Tc(CO(3))(OH)(3)(-) + H(+) with -log(10)[H(+)](1/2) = 8.69 +/- 0.20, which is consistent with the -8.3 +/- 0.6 corresponding hydrolysis constant of the NEA TDB review. 733 +/- 44 mV/SHE and 575 +/- 60 mV/SHE are measured for the standard potentials of the TcO(4)(-)/Tc(CO(3))(OH)(2), and for the TcO(4)(-)/Tc(CO(3))(OH)(3)(-) redox couples respectively. The corresponding formation constants from TcO(OH)(2) are log(10)K(1,2) = 19.8 +/- 0.5 and log(10)K(1,3) = 10.5 +/- 0.5, to be compared with the 19.3 +/- 0.3 and 11.0 +/- 0.6 values proposed by the NEA TDB review. Note that these values have been converted for the formation reactions described here, thus the given values are not those of the NEA TDB review. However, Tc(CO(3))(OH)(2) is predicted to dominate over a surprisingly large range of chemical conditions. The monomeric character of the Tc(IV) complexes is verified in this study.

One step purification process for no-carrier-added (64)Cu produced using enriched nickel target

Abstract Copper-64 has found many applications in positron emission tomography (PET). Its half-life allows to use it for dosimetric studies associated to copper-67 targeted radiotherapy in cancer treatment. The use of 64Ni(p,n)64Cu nuclear reaction is known to produce 64Cu in large amount and with a high specific activity. In this study, targets were obtained by electroplating onto a gold backing and a typical target irradiation uses 200ߙnA, 17ߙMeV protons during 30ߙmin. After irradiation, pure copper-64 is obtained using only one chromatographic column. Nickel-64 is removed in a first elution step and cobalt isotopes in a second one. The extraction yield for copper-64 is 9±23% and nickel and cobalt impurities are under the detection limit. A recovery process of nickel-64 has also been developed.

Effect of aqueous acetic, oxalic and carbonic acids on the adsorption of uranium(VI) onto α-alumina

The prediction of the migration for radionuclides in geologic media requires a quantitative knowledge of retardation phenomena. For this purpose, the sorption of U(VI) onto a model mineral-–α-alumina—is studied here, including the effects of groundwater chemistry: pH and concentrations of small organic ligands (acetate, oxalate and carbonate anions). This work presents experimental evidence for the synergic sorption of uranium(VI) and the small organic ligands, namely sorption of cationic complexes onto alumina. Conversely, since its neutral and anionic complexes were not sorbed, U(VI) cation could also be desorbed as a result of the formation of neutral or anionic complexes in the aqueous phase. By using the ion-exchange theory, and a corresponding restricted set of parameters—exchange capacities and thermodynamic equilibrium constants—the whole set of sorption experiments of U(VI) cationic species onto the α-alumina was modelled under various chemical conditions.

Advances on the Determination of the Astatine Pourbaix Diagram: Predomination of AtO(OH)2− over At− in Basic Conditions

It is generally assumed that astatide (At(-) ) is the predominant astatine species in basic aqueous media. This assumption is questioned in non-complexing and non-reductive aqueous solutions by means of high-pressure anion-exchange chromatography. Contrary to what is usually believed, astatide is found to be a minor species at pH=11. A different species, which also bears a single negative charge, becomes predominant when the pH is increased beyond 7. Using competition experiments, an equilibrium constant value of 10(-6.9) has been determined for the formation of this species from AtO(OH) with the exchange of one proton. The identification of this species, AtO(OH)2 (-) , is achieved through relativistic quantum mechanical calculations, which rule out the significant formation of the AtO2 (-) species, while leading to a hydrolysis constant of AtO(OH) in excellent agreement with experiment when the AtO(OH)2 (-) species is considered. Beyond the completion of the Pourbaix diagram of astatine, this new information is of interest for the development of (211) At radiolabeling protocols.

Alpha-Emitters for Immuno-Therapy: A Review of Recent Developments from Chemistry to Clinics

Alpha-particles are of considerable growing interest for Targeted Alpha Therapy (TAT). TAT gains more attention as new targets, chemical labeling techniques and α-particle emitters are developed but translation of TAT into the clinic has been slow, in part because of the limited availability and the short physical half-lives of some of the available α-particle emitters. This article is an up-to-date overview of the literature concerning α-emitters used for TAT of cancer. It briefly describes the nuclear characteristics, the production parameters (targets, extraction and purification), the complexation properties of these radionuclides to chelates and biological vectors and finally draws-upon the preclinical and clinical studies that have been performed over the past two decades. Radiobiology and dosimetry aspects are also presented in this paper.

Cyclam te1pa for 64 Cu PET imaging. Bioconjugation to antibody, radiolabeling and preclinical application in xenografted colorectal cancer

te1pa is a monopicolinate cyclam previously presented as a better 64 Cu chelator than dota, nota and other chelators with an improved biodistribution and in vivo resistance to transchelation. This study aimed to determine whether te1pa could improve the in vivo stability of 64 Cu chelation concerning radioimmunoconjugates in order to obtain better contrast in PET imaging. te1pa was activated on its remaining acid function to obtain a N-hydroxysulfosuccinimide ester and was then conjugated to the F6 mouse IgG1a (F6 mAb), directed against CEA (carcinoembryonic antigen), leading to the F6-te1pa immunoconjugate. F6-te1pa was compared to F6–C-dota, i.e. F6 mAb conjugated with a C-functionalized dota which is the only chelator used nowadays in preclinical trials for 64 Cu PET imaging. Immunoconjugates were radiolabeled with 64 Cu showing an equivalent conjugation rate of 1 ligand per mAb. The study of the complexation kinetics highlighted a relatively fast process and 64 Cu–F6-te1pa, exhibiting a specific activity of 69.3 AE 28.9 MBq mg A1 , was proved to be inert since only 4.3% of radioactivity was transchelated from the ligand to EDTA (50 000 equiv., overnight) used as a competitor. All these results are comparable with C-functionalized dota. However, in vivo studies carried out in LS174T tumor-bearing nude mice showed a limited transchelation of superoxide dismutase (SOD) into the liver; 1.6% for 64 Cu–F6-te1pa after 24 h post-injection, compared to 4.3% for 64 Cu–F6–C-dota. The uptake of 64 Cu–F6-te1pa in tumors and radioactivity distribution in organs after 24 and 48 h was satisfactory and equivalent to various standards presented in the literature. Finally, PET-phenotypic images obtained with 64 Cu–F6-te1pa at 24 h post-injection showed an excellent contrast between tumors and the healthy tissues around, which agrees well with the results of the biodistribution. The usefulness of te1pa for PET phenotypic imaging using 64 Cu has been validated. The synthesis of a bifunctional derivative of te1pa will be the next step of this work to keep the ligand properties intact.