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Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617

In this study, it was aimed to investigate (149)Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. (149)Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-posit...

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Autores principales: Umbricht, Christoph A., Köster, Ulli, Bernhardt, Peter, Gracheva, Nadezda, Johnston, Karl, Schibli, Roger, van der Meulen, Nicholas P., Müller, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882876/
https://www.ncbi.nlm.nih.gov/pubmed/31780798
http://dx.doi.org/10.1038/s41598-019-54150-w
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author Umbricht, Christoph A.
Köster, Ulli
Bernhardt, Peter
Gracheva, Nadezda
Johnston, Karl
Schibli, Roger
van der Meulen, Nicholas P.
Müller, Cristina
author_facet Umbricht, Christoph A.
Köster, Ulli
Bernhardt, Peter
Gracheva, Nadezda
Johnston, Karl
Schibli, Roger
van der Meulen, Nicholas P.
Müller, Cristina
author_sort Umbricht, Christoph A.
collection PubMed
description In this study, it was aimed to investigate (149)Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. (149)Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. (149)Tb-PSMA-617 was applied at 1 × 6 MBq (Day 0) or 2 × 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 × 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the β(+)-emission of (149)Tb, tumor localization was feasible using PET/CT after injection of (149)Tb-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of (149)Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of (149)Tb for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand’s tissue distribution.
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spelling pubmed-68828762019-12-06 Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617 Umbricht, Christoph A. Köster, Ulli Bernhardt, Peter Gracheva, Nadezda Johnston, Karl Schibli, Roger van der Meulen, Nicholas P. Müller, Cristina Sci Rep Article In this study, it was aimed to investigate (149)Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. (149)Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. (149)Tb-PSMA-617 was applied at 1 × 6 MBq (Day 0) or 2 × 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 × 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the β(+)-emission of (149)Tb, tumor localization was feasible using PET/CT after injection of (149)Tb-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of (149)Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of (149)Tb for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand’s tissue distribution. Nature Publishing Group UK 2019-11-28 /pmc/articles/PMC6882876/ /pubmed/31780798 http://dx.doi.org/10.1038/s41598-019-54150-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Umbricht, Christoph A.
Köster, Ulli
Bernhardt, Peter
Gracheva, Nadezda
Johnston, Karl
Schibli, Roger
van der Meulen, Nicholas P.
Müller, Cristina
Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title_full Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title_fullStr Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title_full_unstemmed Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title_short Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617
title_sort alpha-pet for prostate cancer: preclinical investigation using (149)tb-psma-617
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882876/
https://www.ncbi.nlm.nih.gov/pubmed/31780798
http://dx.doi.org/10.1038/s41598-019-54150-w
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