Expanding the Scope of Pyclen-Picolinate Lanthanide Chelates to Potential Theranostic Applications
Gwladys Nizou, Chiara Favaretto, Francesca Borgna, Pascal V. Grundler, Nathalie Saffon‐Merceron, Carlos Platas‐Iglesias, Olivier Fougère, Olivier Rousseaux, Nicholas P. van der Meulen, Cristina Müller, Maryline Beyler, Raphaël Tripier
Abstract
A family of three picolinate pyclen-based ligands, previously investigated for the complexation of Y3+ and some lanthanide ions (Gd3+, Eu3+), was studied with 161Tb and 177Lu in view of potential radiotherapeutic applications. The set of six Tb3+ and Lu3+ complexes was synthesized and fully characterized. The coordination properties in the solid state and in solution were thoroughly studied. Potentiometric titrations, supported by density functional theory (DFT) calculations, showed the very high stability constants of the Tb3+ and Lu3+ complexes, associated with remarkable kinetic inertness for up to 30 days in 1 M HCl. A complete radiolabeling study performed with both 161Tb and 177Lu radionuclides, including experiments with regard to the stability with and without scavengers and kinetic inertness using challenging agents, proved that the ligands could reasonably compete with the DOTA analogue. To conclude, the potential of using the same ligand for both radiotherapy and optical imaging was highlighted for the first time.