Tolerability of [161Tb]Tb-SibuDAB in comparison to other PSMA-targeting radioligands in the preclinical setting
8 affiliations
- 1Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
- 2PSI Center for Life Sciences, Villigen‑PSI, Switzerland
- 3AnaPath Services Ltd, Liestal, Switzerland
- 4Department of Medical Radiation Sciences, Institution of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- 5Department of Medical Physics and Biomedical Engineering (MFT), Sahlgrenska University Hospital, Gothenburg, Sweden
- 6PSI Center for Nuclear Engineering and Sciences, Villigen‑PSI, Switzerland
- 7Institut Laue-Langevin, Grenoble, France
- 8Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
Abstract
Purpose: The successful preclinical efficacy studies prompted a Phase I clinical trial to investigate [161Tb]Tb-SibuDAB. Deeper insight into potential undesired effects on normal tissues and organs remained to be investigated. The aim of this preclinical study was, therefore, to assess and compare the tolerability of [161Tb]Tb-SibuDAB with that of [177Lu]Lu-SibuDAB, [161Tb]Tb-PSMA-I&T and [177Lu]Lu-PSMA-I&T.
Methods: The time-dependent tissue distribution profiles of [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T were assessed in immunocompetent mice for dosimetry estimations. Substructural activity distribution in kidneys was further investigated ex vivo. In Study I, [161Tb]Tb-SibuDAB, [177Lu]Lu-SibuDAB, [161Tb]Tb-PSMA-I&T and [177Lu]Lu-PSMA-I&T were administered at 30 MBq/mouse while in Study II, additional activities of 15 MBq and 60 MBq [161Tb]Tb-SibuDAB were applied. Blood cell counts were determined on Days 10, 28 and 56 after radioligand injection while blood and bone marrow smears, blood plasma biomarkers and selected organs were investigated at study end on Day 56.
Results: Organ uptake and absorbed doses were severalfold higher for SibuDAB than for PSMA-I&T and terbium-161 delivered about 40% higher organ doses than lutetium-177. Kidney accumulation of radioligands was mainly localized in the renal cortex and blockable with excess ligand in the case of PSMA-I&T but not for SibuDAB. In Study I, leukocyte and erythrocyte levels remained comparable between treated and control mice. Thrombocyte counts remained stable with PSMA-I&T radioligands, while SibuDAB radioligands caused 23–28% decrease by Day 10, with full recovery seen for [161Tb]Tb-SibuDAB. In Study II, 60 MBq [161Tb]Tb-SibuDAB did not significantly reduce leukocyte levels, but erythrocyte counts were marginally lower on Days 10 and 28. Thrombocytes decreased to 18%, 23% and 44% of control values on Day 10 after application of 15 MBq, 30 MBq and 60 MBq, respectively. Thrombocyte counts recovered over time, although average values in some groups remained modestly decreased on Day 56. In both studies, blood plasma biomarkers were similar between treated and control groups. Histological assessment of bone marrow, spleen, liver and kidney showed only minimal alterations (score ≤ 1/3).
Conclusion: Hematological changes were transient, but more pronounced after the application of SibuDAB than of PSMA-I&T, most likely due to the prolonged blood circulation. Other organs and tissues remained unaffected by any of the applied treatments. Substituting lutetium-177 with terbium-161 did not significantly alter the measured parameters. It remains to be demonstrated clinically whether 161Tb-based radioligands can be administered at activity levels comparable to their 177Lu-based analogues.
Graphical abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08129-1.
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BibTeX
@article{krieger2026tolerability,
title = {{Tolerability of [161Tb]Tb-SibuDAB in comparison to other PSMA-targeting radioligands in the preclinical setting}},
author = {Korbinian Krieger and Ana Katrina Mapanao and Julie Bolcaen and Kristel Kegler and Peter Bernhardt and Nicholas P. van der Meulen and Ulli Köster and Alin Chirindel and Guillaume P. Nicolas and Roger Schibli and Cristina Müller},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
year = {2026},
month = aug,
doi = {10.1007/s00259-026-08129-1},
url = {https://doi.org/10.1007/s00259-026-08129-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tolerability of [161Tb]Tb-SibuDAB in comparison to other PSMA-targeting radioligands in the preclinical setting
AU - Korbinian Krieger
AU - Ana Katrina Mapanao
AU - Julie Bolcaen
AU - Kristel Kegler
AU - Peter Bernhardt
AU - Nicholas P. van der Meulen
AU - Ulli Köster
AU - Alin Chirindel
AU - Guillaume P. Nicolas
AU - Roger Schibli
AU - Cristina Müller
PY - 2026
DA - 2026/08/13
JO - European Journal of Nuclear Medicine and Molecular Imaging
DO - 10.1007/s00259-026-08129-1
UR - https://doi.org/10.1007/s00259-026-08129-1
AB - Purpose: The successful preclinical efficacy studies prompted a Phase I clinical trial to investigate [161Tb]Tb-SibuDAB. Deeper insight into potential undesired effects on normal tissues and organs remained to be investigated. The aim of this preclinical study was, therefore, to assess and compare the tolerability of [161Tb]Tb-SibuDAB with that of [177Lu]Lu-SibuDAB, [161Tb]Tb-PSMA-I&T and [177Lu]Lu-PSMA-I&T. Methods: The time-dependent tissue distribution profiles of [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T were assessed in immunocompetent mice for dosimetry estimations. Substructural activity distribution in kidneys was further investigated ex vivo. In Study I, [161Tb]Tb-SibuDAB, [177Lu]Lu-SibuDAB, [161Tb]Tb-PSMA-I&T and [177Lu]Lu-PSMA-I&T were administered at 30 MBq/mouse while in Study II, additional activities of 15 MBq and 60 MBq [161Tb]Tb-SibuDAB were applied. Blood cell counts were determined on Days 10, 28 and 56 after radioligand injection while blood and bone marrow smears, blood plasma biomarkers and selected organs were investigated at study end on Day 56. Results: Organ uptake and absorbed doses were severalfold higher for SibuDAB than for PSMA-I&T and terbium-161 delivered about 40% higher organ doses than lutetium-177. Kidney accumulation of radioligands was mainly localized in the renal cortex and blockable with excess ligand in the case of PSMA-I&T but not for SibuDAB. In Study I, leukocyte and erythrocyte levels remained comparable between treated and control mice. Thrombocyte counts remained stable with PSMA-I&T radioligands, while SibuDAB radioligands caused 23–28% decrease by Day 10, with full recovery seen for [161Tb]Tb-SibuDAB. In Study II, 60 MBq [161Tb]Tb-SibuDAB did not significantly reduce leukocyte levels, but erythrocyte counts were marginally lower on Days 10 and 28. Thrombocytes decreased to 18%, 23% and 44% of control values on Day 10 after application of 15 MBq, 30 MBq and 60 MBq, respectively. Thrombocyte counts recovered over time, although average values in some groups remained modestly decreased on Day 56. In both studies, blood plasma biomarkers were similar between treated and control groups. Histological assessment of bone marrow, spleen, liver and kidney showed only minimal alterations (score ≤ 1/3). Conclusion: Hematological changes were transient, but more pronounced after the application of SibuDAB than of PSMA-I&T, most likely due to the prolonged blood circulation. Other organs and tissues remained unaffected by any of the applied treatments. Substituting lutetium-177 with terbium-161 did not significantly alter the measured parameters. It remains to be demonstrated clinically whether 161Tb-based radioligands can be administered at activity levels comparable to their 177Lu-based analogues. Graphical abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08129-1.
SN - 1619-7070
SN - 1619-7089
ER -