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.
Regino
Celeste Aida S
CA
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
Ogawa
Mikako
M
Alford
Raphael
R
Wong
Karen J
KJ
Kosaka
Noboyuki
N
Williams
Mark
M
Feild
Brian J
BJ
Takahashi
Masatoshi
M
Choyke
Peter L
PL
Kobayashi
Hisataka
H
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
D005456:Fluorescent Dyes; D011975:Receptors, Mitogen; D012235:Rhodamines; D012709:Serum Albumin; D005688:Galactosamine; D005947:Glucose; D005944:Glucosamine