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Article

A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer

1
Department of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
2
Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
3
Department of Radiopharmaceutical Development, German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany and German Cancer Research Center, 69120 Heidelberg, Germany
4
Department of Optical Nanoscopy, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany
5
Department of Nuclear Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany
6
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
7
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, 01328 Dresden, Germany
8
German Cancer Consortium (DKTK), Partner Site Dresden, 01328 Dresden, Germany
9
School of Science, Faculty of Chemistry and Food Chemistry, Technical University Dresden, 01069 Dresden, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Irina Velikyan
Pharmaceuticals 2022, 15(3), 267; https://doi.org/10.3390/ph15030267
Received: 22 December 2021 / Revised: 8 February 2022 / Accepted: 17 February 2022 / Published: 22 February 2022
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
The development of PSMA-targeting low-molecular-weight hybrid molecules aims at advancing preoperative imaging and accurate intraoperative fluorescence guidance for improved diagnosis and therapy of prostate cancer. In hybrid probe design, the major challenge is the introduction of a bulky dye to peptidomimetic core structures without affecting tumor-targeting properties and pharmacokinetic profiles. This study developed a novel class of PSMA-targeting hybrid molecules based on the clinically established theranostic agent PSMA-617. The fluorescent dye-bearing candidates of the strategically designed molecule library were evaluated in in vitro assays based on their PSMA-binding affinity and internalization properties to identify the most favorable hybrid molecule composition for the installation of a bulky dye. The library’s best candidate was realized with IRDye800CW providing the lead compound. Glu-urea-Lys-2-Nal-Chx-Lys(IRDye800CW)-DOTA (PSMA-927) was investigated in an in vivo proof-of-concept study, with compelling performance in organ distribution studies, PET/MRI and optical imaging, and with a strong PSMA-specific tumor uptake comparable to that of PSMA-617. This study provides valuable insights about the design of PSMA-targeting low-molecular-weight hybrid molecules, which enable further advances in the field of peptidomimetic hybrid molecule development. View Full-Text
Keywords: PSMA; hybrid molecules; prostate cancer; guided surgery; theranostics PSMA; hybrid molecules; prostate cancer; guided surgery; theranostics
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MDPI and ACS Style

Eder, A.-C.; Matthias, J.; Schäfer, M.; Schmidt, J.; Steinacker, N.; Bauder-Wüst, U.; Domogalla, L.-C.; Roscher, M.; Haberkorn, U.; Eder, M.; Kopka, K. A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer. Pharmaceuticals 2022, 15, 267. https://doi.org/10.3390/ph15030267

AMA Style

Eder A-C, Matthias J, Schäfer M, Schmidt J, Steinacker N, Bauder-Wüst U, Domogalla L-C, Roscher M, Haberkorn U, Eder M, Kopka K. A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer. Pharmaceuticals. 2022; 15(3):267. https://doi.org/10.3390/ph15030267

Chicago/Turabian Style

Eder, Ann-Christin, Jessica Matthias, Martin Schäfer, Jana Schmidt, Nils Steinacker, Ulrike Bauder-Wüst, Lisa-Charlotte Domogalla, Mareike Roscher, Uwe Haberkorn, Matthias Eder, and Klaus Kopka. 2022. "A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer" Pharmaceuticals 15, no. 3: 267. https://doi.org/10.3390/ph15030267

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