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

Aeli P. Olson; Briana R. Schrage; Md Faizul Islam; Lesta S. Fletcher; Francesca Verich; Morgan A. Dierolf; Eduardo Aluicio-Sarduy; Kaelyn V. Becker; Darren M. Driscoll; Nidhi Girish; Megan E. Simms; Vilmos Kertesz; Frankie D. White; Eszter Boros; Alexander S. Ivanov; Jonathan W. Engle; Nikki A. Thiele

doi:10.1002/anie.202423878

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

Aeli P. Olson, Briana R. Schrage, Md Faizul Islam, Lesta S. Fletcher, Francesca Verich, Morgan A. Dierolf, Eduardo Aluicio-Sarduy, Kaelyn V. Becker, Darren M. Driscoll, Nidhi Girish, Megan E. Simms, Vilmos Kertesz, Frankie D. White, Eszter Boros, Alexander S. Ivanov, Jonathan W. Engle, Nikki A. Thiele

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e202423878
Journal	Angewandte Chemie - International Edition
Volume	64
Issue number	15
DOIs	https://doi.org/10.1002/anie.202423878
State	Published - Apr 7 2025

Funding

This research is supported by the U.S. Department of Energy (DOE) Isotope Program, managed by the Office of Science for Isotope R&D and Production. Additionally, N.G. acknowledges support from the U.S. DOE, Office of Science, Office of Workforce Development for Teachers and Scientists (WDTS) under the Science Undergraduate Laboratory Internships Program (SULI). A.P.O. gratefully acknowledges support from the National Institutes of Health (NIH) under the Ruth L Kirschstein Predoctoral Individual National Research Service Award F31CA239617. J.W.E. and A.P.O. thank the NIH National Cancer Institute for support under award number P01CA250972. This research used 8-ID (ISS) beamline of the National Synchrotron Light Source II, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract No. DE-SC0012704. This research also used resources of the Oak Ridge Leadership Computing Facility (OLCF) at Oak Ridge National Laboratory. This work has been authored by UT-Battelle, LLC, under Contract DE-AC05-00OR22725 with the U.S. DOE. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for U.S. Government purposes. The DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). This research is supported by the U.S. Department of Energy (DOE) Isotope Program, managed by the Office of Science for Isotope R&D and Production. Additionally, N.G. acknowledges support from the U.S. DOE, Office of Science, Office of Workforce Development for Teachers and Scientists (WDTS) under the Science Undergraduate Laboratory Internships Program (SULI). A.P.O. gratefully acknowledges support from the National Institutes of Health (NIH) under the Ruth L Kirschstein Predoctoral Individual National Research Service Award F31CA239617. J.W.E. and A.P.O. thank the NIH National Cancer Institute for support under award number P01CA250972. This research used 8\u2010ID (ISS) beamline of the National Synchrotron Light Source II, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract No. DE\u2010SC0012704. This research also used resources of the Oak Ridge Leadership Computing Facility (OLCF) at Oak Ridge National Laboratory. This work has been authored by UT\u2010Battelle, LLC, under Contract DE\u2010AC05\u201000OR22725 with the U.S. DOE. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a non\u2010exclusive, paid\u2010up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for U.S. Government purposes. The DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( http://energy.gov/downloads/doe\u2010public\u2010access\u2010plan ).

Keywords

antimony
cancer
chelates
radiopharmaceuticals
targeted Auger therapy

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10.1002/anie.202423878

Cite this

Olson, A. P., Schrage, B. R., Islam, M. F., Fletcher, L. S., Verich, F., Dierolf, M. A., Aluicio-Sarduy, E., Becker, K. V., Driscoll, D. M., Girish, N., Simms, M. E., Kertesz, V., White, F. D., Boros, E., Ivanov, A. S., Engle, J. W., & Thiele, N. A. (2025). Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics. Angewandte Chemie - International Edition, 64(15), Article e202423878. https://doi.org/10.1002/anie.202423878

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abstract = "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.",

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author = "Olson, {Aeli P.} and Schrage, {Briana R.} and Islam, {Md Faizul} and Fletcher, {Lesta S.} and Francesca Verich and Dierolf, {Morgan A.} and Eduardo Aluicio-Sarduy and Becker, {Kaelyn V.} and Driscoll, {Darren M.} and Nidhi Girish and Simms, {Megan E.} and Vilmos Kertesz and White, {Frankie D.} and Eszter Boros and Ivanov, {Alexander S.} and Engle, {Jonathan W.} and Thiele, {Nikki A.}",

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Olson, AP, Schrage, BR, Islam, MF, Fletcher, LS, Verich, F, Dierolf, MA, Aluicio-Sarduy, E, Becker, KV, Driscoll, DM, Girish, N, Simms, ME , Kertesz, V , White, FD, Boros, E, Ivanov, AS, Engle, JW & Thiele, NA 2025, 'Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics', Angewandte Chemie - International Edition, vol. 64, no. 15, e202423878. https://doi.org/10.1002/anie.202423878

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T1 - Towards the Stable Chelation of Radioantimony(V) for Targeted Auger Theranostics

AU - Olson, Aeli P.

AU - Schrage, Briana R.

AU - Islam, Md Faizul

AU - Fletcher, Lesta S.

AU - Verich, Francesca

AU - Dierolf, Morgan A.

AU - Aluicio-Sarduy, Eduardo

AU - Becker, Kaelyn V.

AU - Driscoll, Darren M.

AU - Girish, Nidhi

AU - Simms, Megan E.

AU - Kertesz, Vilmos

AU - White, Frankie D.

AU - Boros, Eszter

AU - Ivanov, Alexander S.

AU - Engle, Jonathan W.

AU - Thiele, Nikki A.

PY - 2025/4/7

Y1 - 2025/4/7

N2 - 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.

AB - 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.

KW - antimony

KW - cancer

KW - chelates

KW - radiopharmaceuticals

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JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 15

M1 - e202423878

ER -

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

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