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

Autor: Derks YHW; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands. yvonne.derks@radboudumc.nl., Schilham MGM; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands.; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.; Prosper Prostate Cancer Clinics, Nijmegen, The Netherlands., Rijpkema M; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Smeets EMM; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Amatdjais-Groenen HIV; Institute for Molecules and Materials, Systems Chemistry, Radboud University Nijmegen, Nijmegen, The Netherlands., Kip A; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., van Lith SAM; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., van de Kamp J; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Sedelaar JPM; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.; Prosper Prostate Cancer Clinics, Nijmegen, The Netherlands., Somford DM; Prosper Prostate Cancer Clinics, Nijmegen, The Netherlands.; Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands., Simons M; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Laverman P; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Gotthardt M; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Löwik DWPM; Institute for Molecules and Materials, Systems Chemistry, Radboud University Nijmegen, Nijmegen, The Netherlands., Heskamp S; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands., Lütje S; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands.; Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2023 Jul; Vol. 50 (9), pp. 2872-2884. Date of Electronic Publication: 2023 Apr 15.
DOI: 10.1007/s00259-023-06224-1
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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