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

• Published in: Journal of medicinal chemistry 2010-02, Vol.53 (4), p.1579-1586
• Main Authors: Regino, Celeste Aida S, Ogawa, Mikako, Alford, Raphael, Wong, Karen J, Kosaka, Noboyuki, Williams, Mark, Feild, Brian J, Takahashi, Masatoshi, Choyke, Peter L, Kobayashi, Hisataka
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Female; Fluorescent Dyes - chemistry; Fluorescent Dyes - metabolism; Galactosamine - chemistry; Galactosamine - metabolism; Glucosamine - chemistry; Glucosamine - metabolism; Glucose; Glycosylation; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Miscellaneous. Technology; Neoplasm Transplantation; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peritoneal Cavity; Peritoneal Neoplasms - diagnosis; Peritoneal Neoplasms - metabolism; Peritoneal Neoplasms - pathology; Protein Binding; Receptors, Mitogen - metabolism; Rhodamines - chemistry; Rhodamines - metabolism; Serum Albumin - chemistry; Serum Albumin - metabolism; Tissue Distribution; Transplantation, Heterologous
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/jm901228u

An optical probe, RG-(gal)28GSA, was synthesized to improve the detection of peritoneal implants by targeting the β-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)28GSA, RG-(gal)20GSA, glucose-analogue RG-(glu)28GSA, 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)28GSA using Balb/c mice reveal no toxic effects up to 100× of the standard imaging dose of 1 mg/kg administered either intraperitoneally or intravenously. These data indicate that RG-(gal)28GSA 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.