Design and Preclinical Evaluation of Novel uPAR-Targeting Radiopeptides Modified with an Albumin-Binding Entity.

ABSTRACT: Several studies have focused on the development and application of radiolabeled DOTA-AE105 for targeting the urokinase-type plasminogen activator receptor (uPAR), which is expressed on various cancer types. The aim of this project was to design and evaluate novel uPAR-targeting radiopeptides with improved pharmacokinetic properties in view of their therapeutic application. Five peptides (uPAR-01, uPAR-02, uPAR-03, uPAR-04, and uPAR-05) were synthesized based on the AE105 peptide backbone, a DOTA chelator, and the 4-(p-iodophenyl)butanoate moiety as an albumin binder. The peptides were obtained in 20-29 synthetic steps using solid-phase peptide synthesis with a 6-34% overall yield. In saline, the ¹⁷⁷Lu-labeled peptides (100 MBq/nmol) were stable (>93% intact radiopeptides)

SUBMITTER: Beyer D 

PROVIDER: S-EPMC12135066 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature