Towards New Spectroscopic Tools for Detection of Bonding Properties in Radiopharmaceuticals: Application on La Used as a Homolog of Ac

In recent years, the use of radiopharmaceuticals based on alpha-particle emitting radionuclides has seen considerable growth. In pre-clinical research and first clinical trials, targeted alpha therapy has shown great potential. However, there are still many challenges in this field, one being the need for tight chelation of the alpha-emitting radionuclides and their daughters. We aim to understand the relationships between the bonding properties and bond stability of such compounds.
The recently evolved high-energy resolution X-ray absorption near edge structure (HR-XANES) spectroscopy has proven to be a valuable tool for studying the electronic structure of radionuclides [1,2]. Here, we employ it first to study the bonding properties of lanthanum (La), a homolog of actinium (Ac), with different ligands discussed as nuclide binding sites in radiopharmaceuticals for targeted alpha treatment. La3+ in an aqueous solution, La3+ in buffer media, [La(DOTA)(H2O)]1-, [La(MACROPA)]1+, and [La(PSMA-617)(H2O)] have been prepared and characterized. We measured La L2-edge HR-XANES spectra at the KIT Light Source. Additionally, density functional theory (DFT) and finite difference method near-edge structure (FDMNES) calculations were used to compute the spectra. ... mehrBonding interactions were evaluated using natural orbitals for chemical valence (NOCV) and quantum theory of atoms in molecules (QTAIM), which describe the topology (i.e., shape and magnitude) of the electron density between two bonded atoms. Several spectroscopic and theoretical tools were developed to characterize the covalency of the La-ligand bond. Combined, obtained results are the first steps towards developing new spectroscopic tools that will help understand the electronic structure and bonding, potentially aiding in the design of new chelating ligands for use in radiopharmaceuticals for targeted alpha therapy.