Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics

Antimony-119 (¹¹⁹Sb) is one of the most attractive Auger-electron emitters identified to date, but it remains practically unexplored for targeted radiotherapy because no chelators have been identified to stably bind this metalloid in vivo. In a departure from current studies focused on chelator development for Sb(III), we explore the chelation chemistry of Sb(V) using the tris-catecholate ligand TREN-CAM. Through a combination of radiolabeling, spectroscopic, solid-state, and computational studies, the radiochemistry and structural chemistry of TREN-CAM with ^1XX/natSb(V) were established. The resulting [^1XXSb]Sb-TREN-CAM complex remained intact for several days in human serum, signifying high stability under biological conditions. Finally, the first in vivo single photon emission computed tomography and positron emission tomography imaging studies were carried out using ¹¹⁷Sb, the diagnostic analogue of ¹¹⁹Sb. These studies revealed marked differences in the uptake and distribution of activity in mice administered unchelated [¹¹⁷Sb]Sb(OH)₆ ^- versus [¹¹⁷Sb]Sb-TREN-CAM, suggesting that ¹¹⁷Sb is largely retained by TREN-CAM over the time course of the study. Collectively, these findings demonstrate the most physiologically stable complex of no-carrier-added ^1XXSb yet reported, offering new promise for the clinical implementation of radioantimony in nuclear medicine. Our results also establish the feasibility of ¹¹⁷Sb as an elementally matched partner to ¹¹⁹Sb for theranostic applications.