Towards 213Bi alpha-therapeutics and beyond: unravelling the foundations of efficient BiIII complexation by DOTP. Issue 16 (19th July 2021) - Horváth, Dávid
Abstract : Bi III -DOTP complex is characterised by a fast formation kinetics, an outstanding thermodynamic stability and an impressive kinetic interness, making Bi III -DOTP an optimal model for the development of targeted α-therapy (TAT) radiopharmaceuticals. Abstract : Bismuth isotopes are attracting increasing attention for their potential applications in diagnostics and therapy. The emerging use of 213 Bi in targeted α-therapy (TAT) is a particularly relevant example because it is available from radionuclide generators. A fast formation of stable Bi III -complexes is important for the safe and efficient preparation of labelled (bio)conjugates. Macrocyclic chelating agents are currently the best choice in terms of stability of the corresponding Bi III -complexes. In this work, a thorough study of the thermodynamics and kinetics of formation of Bi III -DOTP including radio-labelling and the comparison with the congener Bi III -DOTA is undertaken. The Bi III -DOTP complex is characterised by a fast formation kinetics ( k Bi(H2 DOTP) = 0.33 s −1 ), an outstanding thermodynamic stability (log K BiDOTP = 38.67) and an impressive kinetic inertness ( t 1/2 pH=3 = 47 600 h). The results clearly demonstrate that DOTP is a better chelating agent for Bi III both in terms of thermodynamic stability and in terms of kinetics of formation, with clear advantages in the radiolabelling of short-lived bismuth isotopes.