Toward understanding 225Ac3+ radionuclide bonding properties within radiopharmaceuticals: the study of La3+ homologues

In recent years the use of radiopharmaceuticals based on alpa-particle emitting radio nuclides has seen a considerable growth. In recent pre-clinical research and first clinical trials targeted alpha therapy has shown great potential. (ref Martina) However, there are still many challenges in this field, one being the need for tight chelating of the aforementioned alpha-emitting radionuclides and their daughters. We aim to understand relations between bonding properties and bond stability of such compounds.
The recently evolved high-energy resolution X-ray absorption near edge structure (HR-XANES) spectroscopy has been proven a valuable tool for the study of the electronic structure of actinides.1 Here we employ it first to study the bonding properties of La a homolog of Ac with different ligands in discussion as nuclide binding site in radiopharmaceuticals for targeted alpha treatment.
La3+(aq), La3+ in buffer media, La - DOTA, La - MACROPA and La - PSMA, have been prepared and characterized. We measured La L2-edge HR-XANES spectra at the Synchrotron Laboratory for Environmental Studies (SUL-X) beamline and La L3-edge extended X-ray absorption fine structure spectroscopa (EXAFS) at the INE beamline at the KIT light source.2,3 Additionally, density functional theory (DFT) and ab initio fine difference method near-edge structure (FDMNS) calculations were used to simulate the spectra.4,5 Bonding interactions were evaluated using natural orbitals for chemical valence (NOCV) and quantum theory of atoms in molecules (QTAIM) which describes the topology (i.e., shape and magnitude) of the electron density between two bonded atoms. ... mehr(Ref Attila)
Several tools (spectroscopic and theoretical) to determine the covalency of the La-ligand bond were developed. One example of this measure can be the comparison of position and shape of the pre- and main absorption edges. EXAFS analysis gave insights into the coordination environment. However, it seems that the near post-edge structure of the HR-XANES might even be more sensitive to differences in local coordination. With QTAIM bond analysis the covalent from the ionic part of the bonding was differentiated. Combined these results are the first steps towards developing new spectroscopic tools that will help understand the electronic structure and the bonding and will potentially affect the design of new chelating ligands with potential use in radiopharmaceuticals for targeted alpha therapy.
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(2) Aran, E. KIT, IPS - SUL-X; last accessed 28.07.2018 https://www.ips.kit.edu/5931.php (accessed Jul 28, 2018).
(3) Rothe, J.; Altmaier, M.; Dagan, R.; Dardenne, K.; Fellhauer, D.; Gaona, X.; Corrales, E. G.-R.; Herm, M.; Kvashnina, K. O.; Metz, V.; Pidchenko, I.; Schild, D.; Vitova, T.; Geckeis, and H. Fifteen Years of Radionuclide Research at the KIT Synchrotron Source in the Context of the Nuclear Waste Disposal Safety Case. Geosciences 2019, 9 (2), 91. https://doi.org/10.3390/geosciences9020091.
(4) Theoretical Chemistry, Vrije Universiteit, Amsterdam, T. N. ADF 2022.1, SCM http://www.scm.com.
(5) Joly, Y. X-ray absorption near-edge structure calculations beyond the muffin-tin approximation. Phys. Rev. B - Condens. Matter Mater. Phys. 2001, 63 (12). https://doi.org/10.1103/PhysRevB.63.125120.