Bioinspired polyhydroxamic sequestering agents for the in vivo decorporation of actinides – ActiDecorp

ActiDecorp is an interdisciplinary French-German project gathering organic, coordination and radiochemists, nuclear toxicologists, physiologists, and pharmacists from 4 complementary teams willing to design decorporating agents able to treat accidental poisoning by actinides (An = U/Np(VI), Np/Pu(IV), Am/Cm(III)). Administered alone or as cocktails, they are sought to be more efficient than Pentetate, CaNa3(DTPA), the sole drug approved by the European Pharmacopeia despite moderate efficacy for Pu-Cm and inefficiency for U-Np. Series of original chelators of various topologies possessing 2 (An(VI)) or 4 (An(III/IV)) cyclic hydroxamate or picolinate (Am/Cm) binding units and their complexes (An, surrogates, biometals) will be prepared and their structures, binding thermodynamics, and electronic properties. Relying on speciation calculations, standardized An-binding assays in serum and in-cellulo toxicity studies, the identified leads will enter preclinical dose-response decorporation tests with rodents (rats).
This comprehensive and complementary approach will ensure a thorough understanding of the proposed ligands’ binding properties on the electronic level, as well as in vitro and in vivo decorporation performances. This will help identify the ideal candidates from a suite of available and envisioned molecules and is expected to help improve comprehension of the removal of highly radiotoxic actinides from the human body in general.