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dc.contributor.author
Müller, Cristina
dc.contributor.author
Umbricht, Christoph A.
dc.contributor.author
Gracheva, Nadezda
dc.contributor.author
Tschan, Viviane J.
dc.contributor.author
Pellegrini, Giovanni
dc.contributor.author
Bernhardt, Peter
dc.contributor.author
Zeevaart, Jan Rijn
dc.contributor.author
Köster, Ulli
dc.contributor.author
Schibli, Roger
dc.contributor.author
van der Meulen, Nicholas P.
dc.date.accessioned
2019-07-23T13:12:36Z
dc.date.available
2019-07-20T02:54:24Z
dc.date.available
2019-07-23T13:12:36Z
dc.date.issued
2019-08
dc.identifier.issn
1619-7070
dc.identifier.issn
1619-7089
dc.identifier.other
10.1007/s00259-019-04345-0
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/354213
dc.identifier.doi
10.3929/ethz-b-000354213
dc.description.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; Eβ͞av = 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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
161Tb
en_US
dc.subject
Auger electrons
en_US
dc.subject
Prostate cancer
en_US
dc.subject
PSMA ligands
en_US
dc.subject
Radioligand therapy
en_US
dc.title
Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-05-27
ethz.journal.title
European Journal of Nuclear Medicine and Molecular Imaging
ethz.journal.volume
46
en_US
ethz.journal.issue
9
en_US
ethz.journal.abbreviated
Eur J Nucl Med Mol Imaging
ethz.pages.start
1919
en_US
ethz.pages.end
1930
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Berlin
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
ethz.date.deposited
2019-07-20T02:54:29Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-07-23T13:12:46Z
ethz.rosetta.lastUpdated
2024-02-02T08:33:33Z
ethz.rosetta.versionExported
true
ethz.COinS
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