Journal Article

DKFZ-2025-02108

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 'Precision on Two Wheels'─Structural Refinement of 64Cu- and 68Ga-Labeled Bicyclic Peptides Targeting Nectin-4 for Improved Tumor Imaging: From Preclinical Development to First-in-Human Application.

Krönke, T. ; Trommer, J. ; Ullrich, M. ; Laube, M. ; Löser, R. ; Kretzschmar, J. ; Urbanova, M. ; Stadlbauer, S. ; Brandt, F. ; Platzek, I. ; Hoberück, S. ; Kotzerke, J. ; Thomas, C. ; Miederer, M. ; Bundschuh, R. A.DKFZ* ; Kopka, K.DKFZ* ; Pietzsch, J. ; Wodtke, R.

2025
ACS Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jmedchem.5c02371

Abstract: The cell adhesion protein nectin-4 emerged as a valid therapeutic target for antibody- and peptide-drug conjugates in cancer. To support patient stratification for such targeted therapies, there is a clinical need for molecular imaging agents capable of quantifying nectin-4 levels noninvasively in vivo. For this purpose, we developed 64Cu- and 68Ga-labeled ligands derived from bicyclic peptide-drug conjugate BT8009. A library of peptides was prepared with a major focus on the bioisosteric replacement of the original methionine residue due to its susceptibility to oxidation. The peptides were characterized for their binding behavior to nectin-4, and radiopharmacological characterization of selected radioligands was performed using urothelial carcinoma cell lines and tumor xenograft models derived thereof. The suitability of the most promising ligand from the preclinical studies, NECT-224, for PET imaging purposes was also demonstrated in a first-in-human application using [68Ga]Ga-NECT-224. The results suggest its further clinical development, but also that of [64Cu]Cu-NECT-224.

Note: 2025 Oct 23;68(20):21962-21987

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Index Chemicus ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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