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A new class of PSMA-617-based hybrid molecules for preoperative imaging and intraoperative fluorescence navigation of prostate cancer

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 pe...

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Hauptverfasser: Eder, Ann-Christin (VerfasserIn) , Matthias, Jessica (VerfasserIn) , Schäfer, Martin (VerfasserIn) , Schmidt, Jana (VerfasserIn) , Steinacker, Nils (VerfasserIn) , Bauder-Wüst, Ulrike (VerfasserIn) , Domogalla, Lisa-Charlotte (VerfasserIn) , Roscher, Mareike (VerfasserIn) , Haberkorn, Uwe (VerfasserIn) , Eder, Matthias (VerfasserIn) , Kopka, Klaus (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 February 2022
In: Pharmaceuticals
Year: 2022, Jahrgang: 15, Heft: 3, Pages: 1-13
ISSN:1424-8247
DOI:10.3390/ph15030267
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ph15030267
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1424-8247/15/3/267
Volltext
Verfasserangaben:Ann-Christin Eder, Jessica Matthias, Martin Schäfer, Jana Schmidt, Nils Steinacker, Ulrike Bauder-Wüst, Lisa-Charlotte Domogalla, Mareike Roscher, Uwe Haberkorn, Matthias Eder and Klaus Kopka
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 12.06.2022
Beschreibung:Online Resource
ISSN:1424-8247
DOI:10.3390/ph15030267

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