"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.

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

SUBMITTER: Kronke T 

PROVIDER: S-EPMC12557367 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature