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. In conclusion, our results also establish the feasibility of 117Sb as an elementally matched partner to 119Sb for theranostic applications.
Olson, Aeli P., Schrage, Briana R., Islam, Md Faizul, Fletcher, Lesta S., Verich, Francesca, Dierolf, Morgan A., Aluicio‐Sarduy, Eduardo, Becker, Kaelyn V., Driscoll, Darren M., Girish, Nidhi, Simms, Megan E., Kertesz, Vilmos, White, Frankie D., Boros, Eszter, Ivanov, Alexander S., Engle, Jonathan W., & Thiele, Nikki A. (2025). Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics. Angewandte Chemie (International Edition), 64(15). https://doi.org/10.1002/anie.202423878
Olson, Aeli P., Schrage, Briana R., Islam, Md Faizul, et al., "Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics," Angewandte Chemie (International Edition) 64, no. 15 (2025), https://doi.org/10.1002/anie.202423878
@article{osti_2573600,
author = {Olson, Aeli P. and Schrage, Briana R. and Islam, Md Faizul and Fletcher, Lesta S. and Verich, Francesca and Dierolf, Morgan A. and Aluicio‐Sarduy, Eduardo and Becker, Kaelyn V. and Driscoll, Darren M. and Girish, Nidhi and others},
title = {Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics},
annote = {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. In conclusion, our results also establish the feasibility of 117Sb as an elementally matched partner to 119Sb for theranostic applications.},
doi = {10.1002/anie.202423878},
url = {https://www.osti.gov/biblio/2573600},
journal = {Angewandte Chemie (International Edition)},
issn = {ISSN 1433-7851},
number = {15},
volume = {64},
place = {United States},
publisher = {Wiley},
year = {2025},
month = {01}}
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); USDOE Office of Science (SC), Nuclear Physics (NP); USDOE Office of Science (SC), Office of Workforce Development for Teachers & Scientists (WDTS)
Grant/Contract Number:
AC05-00OR22725; SC0012704
OSTI ID:
2573600
Alternate ID(s):
OSTI ID: 2514507
Journal Information:
Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 15 Vol. 64; ISSN 1521-3773; ISSN 1433-7851