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Theranostics 2021; 11(4):1527-1541. doi:10.7150/thno.52166 This issue Cite

Research Paper

Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer

Yvonne H.W. Derks1✉, Mark Rijpkema1, Helene I.V. Amatdjais-Groenen2, Annemarie Kip1, Gerben M. Franssen1, J. P. Michiel Sedelaar3,4, Diederik M. Somford4,5, Michiel Simons6, Peter Laverman1, Martin Gotthardt1, Dennis W. P. M. Löwik2, Susanne Lütje7#, Sandra Heskamp1#

1. Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
2. Radboud University Nijmegen, Institute for Molecules and Materials, Systems Chemistry, Nijmegen, The Netherlands.
3. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
4. Prosper Clinics, Nijmegen, The Netherlands.
5. Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
6. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
7. Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
#These authors contributed equally to this work.

✉ Corresponding author: Yvonne Derks, Department of Radiology, Nuclear Medicine and Anatomy; Radboud University Medical Center. Geert Grooteplein Zuid, 10; 6525GA Nijmegen; Phone: +31 (0)24 365 5340; E-mail: yvonne.derksnl.

Citation:
Derks YHW, Rijpkema M, Amatdjais-Groenen HIV, Kip A, Franssen GM, Sedelaar JPM, Somford DM, Simons M, Laverman P, Gotthardt M, Löwik DWPM, Lütje S, Heskamp S. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics 2021; 11(4):1527-1541. doi:10.7150/thno.52166. https://www.thno.org/v11p1527.htm
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Abstract

Graphic abstract

Incomplete resection of prostate cancer (PCa) occurs in 15%-50% of PCa patients. Disease recurrence negatively impacts oncological outcome. The use of radio-, fluorescent-, or photosensitizer-labeled ligands to target the prostate-specific membrane antigen (PSMA) has become a well-established method for the detection and treatment of PCa.

Methods: Here, we developed and characterized multimodal [111In]In-DOTA(GA)-IRDye700DX-PSMA ligands, varying in their molecular composition, for use in intraoperative radiodetection, fluorescence imaging and targeted photodynamic therapy of PCa lesions. PSMA-specificity of these ligands was determined in xenograft tumor models and on fresh human PCa biopsies.

Results: Ligand structure optimization showed that addition of the photosensitizer (IRDye700DX) and additional negative charges significantly increased ligand uptake in PSMA-expressing tumors. Moreover, an ex vivo incubation study on human tumor biopsies confirmed the PSMA-specificity of these ligands on human samples, bridging the gap to the clinical situation.

Conclusion: We developed a novel PSMA-targeting ligand, optimized for multimodal image-guided PCa surgery combined with targeted photodynamic therapy.

Keywords: Prostate-specific membrane antigen, imaging agents, prostate cancer, intraoperative, radiochemistry

Citation styles

APA
Derks, Y.H.W., Rijpkema, M., Amatdjais-Groenen, H.I.V., Kip, A., Franssen, G.M., Sedelaar, J.P.M., Somford, D.M., Simons, M., Laverman, P., Gotthardt, M., Löwik, D.W.P.M., Lütje, S., Heskamp, S. (2021). Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics, 11(4), 1527-1541. https://doi.org/10.7150/thno.52166.

ACS
Derks, Y.H.W.; Rijpkema, M.; Amatdjais-Groenen, H.I.V.; Kip, A.; Franssen, G.M.; Sedelaar, J.P.M.; Somford, D.M.; Simons, M.; Laverman, P.; Gotthardt, M.; Löwik, D.W.P.M.; Lütje, S.; Heskamp, S. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics 2021, 11 (4), 1527-1541. DOI: 10.7150/thno.52166.

NLM
Derks YHW, Rijpkema M, Amatdjais-Groenen HIV, Kip A, Franssen GM, Sedelaar JPM, Somford DM, Simons M, Laverman P, Gotthardt M, Löwik DWPM, Lütje S, Heskamp S. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics 2021; 11(4):1527-1541. doi:10.7150/thno.52166. https://www.thno.org/v11p1527.htm

CSE
Derks YHW, Rijpkema M, Amatdjais-Groenen HIV, Kip A, Franssen GM, Sedelaar JPM, Somford DM, Simons M, Laverman P, Gotthardt M, Löwik DWPM, Lütje S, Heskamp S. 2021. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics. 11(4):1527-1541.

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