For certain radioelements of practical interest, it is necessary to characterize the chemical forms in which they initially occur before their reactivity can be studied. This is particularly true for astatine (Z=85), whose radioisotope 211 exhibits physical characteristics that are highly suitable for use in nuclear medicine. The initial radiolabeling process to produce a radiopharmaceutical is carried out in aqueous solution. By combining the results of (i) two-component relativistic DFT calculations of thermodynamic stability and (ii) measurements of partition coefficients in a biphasic system at the Subatech laboratory (UMR 6457), the elemental species of astatine in aqueous solution were identified (Figure 1). Astatine differs in particular from other halogens in that, in addition to At^-, it exhibits stable cationic forms At⁺ and AtO⁺ under oxidizing conditions and at strongly acidic pH.

Although discovered over a century ago, protactinium (Z=91) remains one of the least well-characterised actinides, particularly when compared with its neighbour uranium (Z=92). Whilst no oxo bond is formed in solution with thorium (Z=90) and two oxo bonds may form with uranium, Pa is thought to form only a single oxo bond. State-of-the art calculations reveal that its bond length is longer than expected (Figure 1), calling into question previous experimental data and confirming the unique nature of Pa amongst the actinides.

One of the promising approaches in nuclear medicine is targeted alpha therapy. Its principle is based on combining a radioactive isotope that emits alpha (α) particles, capable of destroying cells in small tumors and metastatic cancers, with a biological vector that specifically recognizes these cells. This combination is facilitated by a chelating agent (ACB, Figure 2), a molecule that acts as a chemical link to ensure that the radioisotope is not released in vivo. Labeling biomolecules with ²¹¹At or ²²³Ra remains a challenge due to a lack of understanding of the chemistry of these radioelements; for example, the bond formed with ²¹¹At is unstable for most current radiopharmaceutical candidates. Several hypotheses related to the strength of the bonds formed or to astatine’s sensitivity to oxidative processes have been tested through modeling. We recently quantified astatine’s exceptional ability to form intermolecular interactions, known as halogen bonds (Figure 2). The hypothesis that the degradation of radiopharmaceuticals may be initiated by the formation of halogen bonds between astatine and sites found in the biological environment led to the in silico design of a family of compounds, which were subsequently synthesized and evaluated in vitro at the CRCI²NA laboratory (UMR 6075), and then patented (WO2025219558).

The research is expanding to include the design of chelating agents specific to the radioisotope 223 of radium, which is currently the only α emitter approved by authorities (ANSM, FDA), but which are also applicable to the radioisotope 226 that presents specific environmental challenges (contamination of natural areas).