Improving GRPR-targeting peptides for radiotheranostics application: insights from chelator modifications and α-methyl-L tryptophan substitution.

ABSTRACT:

Background

Targeting the gastrin-releasing peptide receptor (GRPR) is a promising approach for radionuclide therapy in prostate and breast cancers. GRPR-targeting peptides often have limited metabolic stability, which can compromise their clinical efficacy due to rapid degradation in the bloodstream, leading to reduced tumor uptake. We previously reported the GRPR-targeting peptide AU-RM26-M2 (DOTAGA-PEG₂-Pip-[Sar¹¹]RM26), which demonstrated promising pharmacokinetics in GRPR-expressing xenografts. In this study, we aimed to enhance the metabolic stability and targeting properties of AU-RM26-M2 by incorporating α-methyl-L-tryptophan (MetTrp) at position 8 in the pharmacophore, and to investigate the influence of chelator choice (DOTAGA vs. DOTA) for labeling w

SUBMITTER: Obeid K 

PROVIDER: S-EPMC12615863 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature