Cages molecules for sequestration of Astatide – CAMERA

CAMERA proposal aims to give access to innovative radiopharmaceuticals labelled with 211 Astatine, an alpha-emitter very promising for use in nuclear medicine. At-labelled compounds are generally prepared using C-At covalent bonds that are not very stable which is detrimental for their use in biological applications. Other modality of bonding are needed to prepare more stable At-labelled compounds. For the first time, we wish to sequester Astatide anion (At-) using non-covalent interactions with high affinity in aqueous media. Cage-molecules displaying unprecedented affinities for Iodide, the halide with closest properties to At, will be choosen for the late-stage complexation of astatide. Cage-molecules will be functionalized with flexible arms able to interact with the encapsulated anions to further increase the stability of the formed complexes in aqueous media. Depending on the chemical functions that will be grafted on the periphery of the cage molecules, these new complexing agents may also be water-soluble and may have a fluorescent group to facilitate their monitoring. In order to maximize stability and selectivity, the synthesis work will be based on ab-initio calculations and extensive structural, thermodynamic and kinetic characterizations. This proposal will give new knowledge in supramolecular chemistry, in the chemistry of host-guest type cage molecules, in complexation of anions and more specially in Astate chemistry and applications. This work will open the way to the development of radiopharmaceuticals based on anion-chelation that are still unknown in contrast with bifunctional metal chelators used for radiometal complexation and bioconjugaison. This project will require effective collaboration between theoretical chemists for the design of cages, organic chemists for their synthesis and radiochemists for manipulations in the presence of radioactive anions and of biologists.