Towards 213Bi alpha-therapeutics and beyond: unravelling the foundations of efficient BiIII complexation by DOTP

Bismuth isotopes are attracting increasing attention for their potential applications in diagnostics and therapy. The emerging use of 213Bi in targeted α-therapy (TAT) is a particularly relevant example because it is available from radionuclide generators. A fast formation of stable BiIII-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 BiIII-complexes. In this work, a thorough study of the thermodynamics and kinetics of formation of BiIII-DOTP including radio-labelling and the comparison with the congener BiIII-DOTA is undertaken. The BiIII-DOTP complex is characterised by a fast formation kinetics (kBi(H2DOTP) = 0.33 s−1), an outstanding thermodynamic stability (log KBiDOTP = 38.67) and an impressive kinetic inertness (t1/2pH=3 = 47 600 h). The results clearly demonstrate that DOTP is a better chelating agent for BiIII both in terms of thermodynamic stability and in terms of kinetics of formation, with clear advantages in the radiolabelling of short-lived bismuth isotopes.

HORVATH David;  TRAVAGIN Fabio;  GUIDOLIN Nicol;  BUONSANTI Federica;  TIRCSÓ Gyula;  TOTH Imre;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  NOTNI Johannes;  GIOVENZANA Giovanni;  BARANYAI Zsolt; 

2021-09-30

ROYAL SOC CHEMISTRY

JRC125023

2052-1553 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC125023,   

10.1039/d1qi00559f (online),