Significant reduction of activity retention in the kidneys via optimized linker sequences in radiohybrid-based minigastrin analogs.

ABSTRACT:

Background

We recently introduced radiohybrid (rh)-based minigastrin analogs e.g., DOTA-rhCCK-18 (DOTA-D-Dap(p-SiFA)-(D-γ-Glu)₈-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH₂), that revealed substantially increased activity retention in the tumor. However, one major drawback of these first generation rh-based cholecystokinin-2 receptor (CCK-2R) ligands is their elevated activity levels in the kidneys, especially at later time points (24 h p.i.). Therefore, this study aimed to reduce kidney retention with regard to a therapeutic use via substitution of negatively charged D-glutamic acid moieties by hydrophilic uncharged polyethylene glycol (PEG) linkers of various length ((PEG)₄ to (PEG)₁₁). Furthermore, the influence of differently charged silicon-based

SUBMITTER: Holzleitner N 

PROVIDER: S-EPMC10907560 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature