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Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand

PURPOSE: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand...

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Autores principales: Derks, Yvonne H. W., Schilham, Melline G. M., Rijpkema, Mark, Smeets, Esther M. M., Amatdjais-Groenen, Helene I. V., Kip, Annemarie, van Lith, Sanne A. M., van de Kamp, Jill, Sedelaar, J. P. Michiel, Somford, Diederik M., Simons, Michiel, Laverman, Peter, Gotthardt, Martin, Löwik, Dennis W. P. M., Heskamp, Sandra, Lütje, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317872/
https://www.ncbi.nlm.nih.gov/pubmed/37060367
http://dx.doi.org/10.1007/s00259-023-06224-1
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author Derks, Yvonne H. W.
Schilham, Melline G. M.
Rijpkema, Mark
Smeets, Esther M. M.
Amatdjais-Groenen, Helene I. V.
Kip, Annemarie
van Lith, Sanne A. M.
van de Kamp, Jill
Sedelaar, J. P. Michiel
Somford, Diederik M.
Simons, Michiel
Laverman, Peter
Gotthardt, Martin
Löwik, Dennis W. P. M.
Heskamp, Sandra
Lütje, Susanne
author_facet Derks, Yvonne H. W.
Schilham, Melline G. M.
Rijpkema, Mark
Smeets, Esther M. M.
Amatdjais-Groenen, Helene I. V.
Kip, Annemarie
van Lith, Sanne A. M.
van de Kamp, Jill
Sedelaar, J. P. Michiel
Somford, Diederik M.
Simons, Michiel
Laverman, Peter
Gotthardt, Martin
Löwik, Dennis W. P. M.
Heskamp, Sandra
Lütje, Susanne
author_sort Derks, Yvonne H. W.
collection PubMed
description PURPOSE: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for (111)In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064). We evaluated the efficacy of PSMA-tPDT using PSMA-N064 in cell viability assays, a mouse xenograft model and in an ex vivo incubation study on fresh human PCa tissue. METHODS: In vitro, therapeutic efficacy of PSMA-N064 was evaluated using PSMA-positive LS174T cells and LS174T wild-type cells. In vivo, PSMA-N064-mediated tPDT was tested in immunodeficient BALB/c mice-bearing PSMA-positive LS174T xenografts. Tumor growth and survival were compared to control mice that received either NIR light or ligand injection only. Ex vivo tPDT efficacy was evaluated in excised fresh human PCa tissue incubated with PSMA-N064. RESULTS: In vitro, tPDT led to a PSMA-specific light- and ligand dose-dependent loss in cell viability. In vivo, tPDT-induced tumor cell apoptosis, delayed tumor growth, and significantly improved survival (p = 0.004) of the treated PSMA-positive tumor-bearing mice compared with the controls. In fresh ex vivo human PCa tissue, apoptosis was significantly increased in PSMA-tPDT-treated samples compared to non-treated control samples (p = 0.037). CONCLUSION: This study showed the feasibility of PSMA-N064-mediated tPDT in cell assays, a xenograft model and excised fresh human PCa tissue. This paves the way to investigate the impact of in vivo PSMA-tPDT on surgical outcome in PCa patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06224-1.
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spelling pubmed-103178722023-07-05 Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand Derks, Yvonne H. W. Schilham, Melline G. M. Rijpkema, Mark Smeets, Esther M. M. Amatdjais-Groenen, Helene I. V. Kip, Annemarie van Lith, Sanne A. M. van de Kamp, Jill Sedelaar, J. P. Michiel Somford, Diederik M. Simons, Michiel Laverman, Peter Gotthardt, Martin Löwik, Dennis W. P. M. Heskamp, Sandra Lütje, Susanne Eur J Nucl Med Mol Imaging Original Article PURPOSE: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for (111)In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064). We evaluated the efficacy of PSMA-tPDT using PSMA-N064 in cell viability assays, a mouse xenograft model and in an ex vivo incubation study on fresh human PCa tissue. METHODS: In vitro, therapeutic efficacy of PSMA-N064 was evaluated using PSMA-positive LS174T cells and LS174T wild-type cells. In vivo, PSMA-N064-mediated tPDT was tested in immunodeficient BALB/c mice-bearing PSMA-positive LS174T xenografts. Tumor growth and survival were compared to control mice that received either NIR light or ligand injection only. Ex vivo tPDT efficacy was evaluated in excised fresh human PCa tissue incubated with PSMA-N064. RESULTS: In vitro, tPDT led to a PSMA-specific light- and ligand dose-dependent loss in cell viability. In vivo, tPDT-induced tumor cell apoptosis, delayed tumor growth, and significantly improved survival (p = 0.004) of the treated PSMA-positive tumor-bearing mice compared with the controls. In fresh ex vivo human PCa tissue, apoptosis was significantly increased in PSMA-tPDT-treated samples compared to non-treated control samples (p = 0.037). CONCLUSION: This study showed the feasibility of PSMA-N064-mediated tPDT in cell assays, a xenograft model and excised fresh human PCa tissue. This paves the way to investigate the impact of in vivo PSMA-tPDT on surgical outcome in PCa patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06224-1. Springer Berlin Heidelberg 2023-04-15 2023 /pmc/articles/PMC10317872/ /pubmed/37060367 http://dx.doi.org/10.1007/s00259-023-06224-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Derks, Yvonne H. W.
Schilham, Melline G. M.
Rijpkema, Mark
Smeets, Esther M. M.
Amatdjais-Groenen, Helene I. V.
Kip, Annemarie
van Lith, Sanne A. M.
van de Kamp, Jill
Sedelaar, J. P. Michiel
Somford, Diederik M.
Simons, Michiel
Laverman, Peter
Gotthardt, Martin
Löwik, Dennis W. P. M.
Heskamp, Sandra
Lütje, Susanne
Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title_full Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title_fullStr Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title_full_unstemmed Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title_short Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand
title_sort imaging and photodynamic therapy of prostate cancer using a theranostic psma-targeting ligand
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317872/
https://www.ncbi.nlm.nih.gov/pubmed/37060367
http://dx.doi.org/10.1007/s00259-023-06224-1
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