Journal Article

DKFZ-2022-00555

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer.

Eder, A.-C. (First author)DKFZ* ; Matthias, J. ; Schäfer, M.DKFZ* ; Geberlein, J.DKFZ* ; Steinacker, N.DKFZ* ; Bauder-Wüst, U.DKFZ* ; Domogalla, L.-C.DKFZ* ; Roscher, M.DKFZ* ; Haberkorn, U.DKFZ* ; Eder, M.DKFZ* ; Kopka, K. (Last author)DKFZ*

2022
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/ph15030267

Abstract: 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.

Keyword(s): PSMA ; guided surgery ; hybrid molecules ; prostate cancer ; theranostics

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Contributing Institute(s):

1. Radiopharmazeutische Chemie (E030)
2. DKTK FR zentral (FR01)
3. E060 KKE Nuklearmedizin (E060)
4. DKTK DD zentral (DD01)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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