Two-step synthesis of galactosylated human serum albumin as a targeted optical imaging agent for peritoneal carcinomatosis.

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 on 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 no 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.