Abstract
Antimony-119 ((119)Sb) 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/nat)Sb(V) were established. The resulting [(1XX)Sb]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 (117)Sb, the diagnostic analogue of (119)Sb. These studies revealed marked differences in the uptake and distribution of activity in mice administered unchelated [(117)Sb]Sb(OH)(6) (-) versus [(117)Sb]Sb-TREN-CAM, suggesting that (117)Sb 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 (1XX)Sb yet reported, offering new promise for the clinical implementation of radioantimony in nuclear medicine. Our results also establish the feasibility of (117)Sb as an elementally matched partner to (119)Sb for theranostic applications.