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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Müller Cristina, Umbricht Christoph A., Gracheva Nadezda, Tschan Viviane J., Pellegrini Giovanni, Bernhardt Peter, Zeevaart Jan Rijn, Köster Ulli, Schibli Roger, van der Meulen Nicholas P.,
Project Translational molecular imaging of neuroendocrine tumours using innovative PET radionuclides
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Original article (peer-reviewed)

Journal European Journal of Nuclear Medicine and Molecular Imaging
Volume (Issue) 46(9)
Page(s) 1919 - 1930
Title of proceedings European Journal of Nuclear Medicine and Molecular Imaging
DOI 10.1007/s00259-019-04345-0

Open Access

URL http://doi.org/10.1007/s00259-019-04345-0
Type of Open Access Publisher (Gold Open Access)

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 (T1/2 = 6.89 days; Eβav = 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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