Two-Step Synthesis of Galactosylated Human Serum Albumin as a Targeted Optical Imaging Agent for Peritoneal Carcinomatosis

摘要

An optical probe, RG-(gal)(28)GSA, was synthesized to improve the detection of peritoneal implants by targeting the beta-D-galactose receptors highly expressed oil the cell surface of a wide variety of cancers arising from the ovary, pancreas, colon, and stomach. Evaluation of RG-(gal)(28)GSA, RG-(gal)(20)GSA, glucose-analogue RG-(glu)(28)GSA, and control RG-HSA demonstrates specificity for the galactose, binding to several human adenocarcinoma cell lines, and cellular internalization. Studies using peritoneally disseminated SHIN3 xenografts in mice also confirmed a preference for galactose with the ability to detect submillimeter size lesions. Preliminary toxicity study for RG-(gal)(28)GSA using Balb/c mice reveal 110 toxic effects up to 100x of the standard imaging dose of 1 mg/kg administered either intraperitoneally or intravenously. These data Indicate that RG-(gal)(28)GSA can selectively target a variety of human adenocarcinomas, can Improve intraoperative or endoscopic tumor detection and resection, and may have little or no toxic in vivo effects hence, it may be clinically translatable.