Review of actinide decorporation with chelating agents

Abstract

In case of accidental release of radionuclides in a nuclear facility or in the environment, internal contamination (inhalation, ingestion or wound) with actinides represents a severe health risk to human beings. It is therefore important to provide effective chelation therapy or decorporation to reduce acute radiation damage, chemical toxicity, and late radiation effects.Speciation governs bioavailability and toxicity of elements and it is a prerequisite tool for the design and success of new ligands or chelating agents. The purpose of this review is to present the state-of-the-art of actinide decorporation within biological media, to recall briefly actinide metabolism, to list the basic constraints of actinideeligand for development, to describe main tools developed and used for decorporation studies, to review mainly the chelating agents tested for actinides, and finally to conclude on the future trends in this field. To cite this article: É. Ansoborlo et al., C. R. Chimie X 33 (2007). Ó 2007 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved. RésuméEn cas de rejet accidentel de radionucléides dans une installation nucléaire ou dans l'environnement, il existe un risque de contamination interne (inhalation, ingestion ou blessure) pour l'homme et il est important de pouvoir fournir un traitement thérapeutique par des agents chélatants ou décorporation permettant de réduire la dose, la toxicité chimique et les effets retardés des radiations.La spéciation domine la biodisponibilité et la toxicité des éléments et représente un outil indispensable pour la conception et l'efficacité de nouveaux ligands ou chélatants. Le but de cet article est de présenter l'état de l'art sur la décorporation des actinides en milieu biologique, de rappeler les grandes lignes du métabolisme des actinides, de lister les contraintes indispensables actinidee

Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

“…By the means of chromatographic studies and competition experiments with iron, the authors reported that the binding site of Th(IV) was the iron-binding site of transferrin (HSTf). Similar behaviour was reported for different actinides (IV) including Pu(IV) from various in vivo and in vitro studies [3,[9][10][11]. The interaction between Th(IV) and HSTf was further studied by Harris et al [12] by using difference ultraviolet spectroscopy (DUS).…”

“…The quantitative description of the interactions of thorium (IV) with blood serum components is of high relevance for the rational design of molecules suitable for in vivo chelation of thorium in medical applications [1,2] or for decorporation in case of accidental ingestion [3][4][5]. In the first case, the chelating agent is used to couple the radionuclide to tumor selective carrier molecules to target and destroy cancer cells [6].…”

The Influence of Linker Geometry in Bis(3‐hydroxy‐N‐methyl‐pyridin‐2‐one) Ligands on Solution Phase Uranyl Affinity

“…It was found that running the titrations only up to pH 8.5 and 9.0, respectively, restored reversibility in the uranyl titrations. The cause of this irreversibility is unknown, but corresponds roughly to additional deprotonation of or continued hydroxide introduction to the [UO 2 Uranyl titrations with all Me-3,2-HOPO ligands displayed a rapid increase in intensity between pH 2 and pH 4, indicating deprotonation of the ligand and complexation of the uranyl cation. For tetradentate ligands (with the exception of L 6 H 2 ), this result was refined as the formation of a UO 2 L(solv.)…”

“…pUO 2 is calculated using standard conditions of [UO 2 2+ ] = 10 -6 M and [L] = 10 -5 M (L:UO 2 2+ = 10), and thus the minimum pUO 2 value is 6.0, at which no metal complexation occurs. While typically reported at physiological pH, pUO 2 can be calculated at any pH once proton and uranyl affinities are known; pUO 2 values at pH 2.5, 7.4 and 8.5 are listed for each Me-3,2-HOPO ligand in Table 4.…”

“…[2] Modifiable ligand properties include ligand geometry, hard/soft character of coordinating atoms, ligand denticity, and geometric pre-organization. Optimization of these design characteristics is observed in bacterial ferric ion shuttling mechanisms, [3,4] but is also central to synthetic compounds applied in many different selective extraction/removal applications such as heavy metal decorporation, [5,6] and iron overload treatment.…”