Optimizing the pharmacokinetics of an ²¹¹At-labeled RGD peptide with an albumin-binding moiety via the administration of an albumin-binding inhibitor.

ABSTRACT:

Purpose

A probe for targeted alpha therapy (TAT) using the RGD peptide (Ga-DOTA-K([²¹¹At]APBA)-c(RGDfK) ([²¹¹At]1)) with albumin-binding moiety (ABM) was recently developed. [²¹¹At]1 highly accumulated in tumors and significantly inhibited tumor growth in U-87 MG tumor-bearing mice. However, high [²¹¹At]1 retention in blood may cause critical adverse events, such as hematotoxicity. Therefore, we attempted to accelerate the blood clearance of [²¹¹At]1 by competitively inhibiting the binding of [²¹¹At]1 to albumin to modulate the pharmacokinetics of the former.

Methods

To evaluate the effects of albumin-binding inhibitors in normal mice, sodium 4-(4-iodophenyl)butanoate at 2, 5, or 10 molar equivalents of blood

SUBMITTER: Echigo H 

PROVIDER: S-EPMC11224111 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature