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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-08-2019 | Prostate Cancer | Original Article

Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer

Authors: Cristina Müller, Christoph A. Umbricht, Nadezda Gracheva, Viviane J. Tschan, Giovanni Pellegrini, Peter Bernhardt, Jan Rijn Zeevaart, Ulli Köster, Roger Schibli, Nicholas P. van der Meulen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2019

Abstract

Purpose

The prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate ¹⁶¹Tb (T_1/2 = 6.89 days; Eβ^͞_av = 154 keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to ¹⁷⁷Lu-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.

Methods

¹⁶¹Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100 MBq/nmol. ¹⁶¹Tb-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for ¹⁷⁷Lu-PSMA-617. The effects of ¹⁶¹Tb-PSMA-617 and ¹⁷⁷Lu-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. ¹⁶¹Tb-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.

Results

¹⁶¹Tb-PSMA-617 and ¹⁷⁷Lu-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to ¹⁶¹Tb-PSMA-617 as compared to the effect obtained with the same activities of ¹⁷⁷Lu-PSMA-617 over the whole investigated concentration range. Treatment of mice with ¹⁶¹Tb-PSMA-617 (5.0 MBq/mouse and 10 MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65 days) compared to untreated control animals (19 days). Therapy studies to compare the effects of ¹⁶¹Tb-PSMA-617 and ¹⁷⁷Lu-PSMA-617 indicated the anticipated superiority of ¹⁶¹Tb over ¹⁷⁷Lu.

Conclusion

¹⁶¹Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to ¹⁷⁷Lu-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of ¹⁶¹Tb. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of ¹⁶¹Tb-PSMA-617 for the treatment of mCRPC.

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Title: Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
Authors: Cristina Müller
Christoph A. Umbricht
Nadezda Gracheva
Viviane J. Tschan
Giovanni Pellegrini
Peter Bernhardt
Jan Rijn Zeevaart
Ulli Köster
Roger Schibli
Nicholas P. van der Meulen
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Radionuclide Therapy
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04345-0

At a glance: The STEP trials

Springer Medicine

Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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