Actinium-225 is an excellent candidate for targeted radiotherapy to treat cancer and infections due to its half-life of ten days and emission of four high-energy alpha particles. In order to harness and direct the energetic potential of actinium, strongly binding chelators must be developed that are capable of retaining actinium ions until they reach the biochemical target. Little work has been done to understand the bonding properties of actinium, making the development of chelating ligands a challenging task. In this talk I will present a systematic theoretical study, done in collaboration with experimentalists, to elucidate the unique bonding properties of macrocyclic chelating agents varying in ring size, coordination number, and functional groups. We first identify the optimal ring size and coordination number of the chelates for actinium binding based on thermodynamic analysis. Using this information, we explore attaching different functional groups to various positions on the rings. We then perform a structure and bonding analysis of proposed chelators to determine which features of chelating molecules are desirable for optimal actinium binding. The fundamental bonding information that is gained for actinium through this study can be used as a driving force in the design process for multifunctional chelators.

Computational design of actinium-225 chelators for use in targeted alpha therapy

2019 Spring National Meeting

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