title: Two-step synthesis of galactosylated human serum albumin as a targeted optical imaging agent for peritoneal carcinomatosis.
abstract: 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.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
authors.forename: Celeste Aida S
authors.initials: CA
authors.lastname: Regino
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Raphael
authors.initials: R
authors.lastname: Alford
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Wong
authors.forename: Noboyuki
authors.initials: N
authors.lastname: Kosaka
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Feild
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D005688:Galactosamine / Q000737:chemistry* / Q000378:metabolism; D005944:Glucosamine / Q000737:chemistry / Q000378:metabolism; D005947:Glucose; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011975:Receptors, Mitogen / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D005456:Fluorescent Dyes; D011975:Receptors, Mitogen; D012235:Rhodamines; D012709:Serum Albumin; D005688:Galactosamine; D005947:Glucose; D005944:Glucosamine