Insights into Actinium Complexes with Tetraacetates RAcBATA versus AcDOTA: Thermodynamic, Structural, and Labeling Properties

A comparative study of the Ac3+ complex withthe tetraacetates H(4)DOTA and H(4)BATA is conducted.The stability constants of both Ac3+ and La3+ complexes are determined, indicating the exceptional thermodynamicstability of the H(4)BATA complexes. The DFT calculationsdemonstrate the inclusion of the La3+ and Ac3+ cations inside the macrocyclic cavity. Finally, the stability ofthe [AcBATA](-) complex in blood serum and in normalmice was established, making the H(4)BATA chelator a possiblecandidate for radiopharmaceuticals. In the current research, we conducteda comparative studyof theAc(3+) complex with H(4)DOTA and H(4)BATA.The stability constants of the [AcBATA](-) and [AcDOTA](-) complexes were studied directly by extraction methods.We discovered that the thermodynamic properties of the [AcBATA](-) complex are superior to those of [AcDOTA](-). Moreover, the fast kinetics of H(4)BATA complexation withAc(3+) during the radiolabeling experiment was observed alreadyat room temperature. Ac3+ was placed inside the macrocycliccavity of the [AcBATA](-) complex, preventing therelease of the cation. According to DFT studies, two possible conformationswere found, where two pendant arms coordinate with the metal cationon one side of the azacrown cavity and two on the other side, or threependant arms are located on one side and one on the other. Finally,high inertness in vitro and in vivo of [AcBATA](-) was discovered, making the H(4)BATA ligand highly preferablefor application as a component of actinium-based radiopharmaceuticals.