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

J Med Chem. 2010 Feb 25;53(4):1579-86. doi: 10.1021/jm901228u.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Galactosamine / chemistry*
  • Galactosamine / metabolism
  • Glucosamine / chemistry
  • Glucosamine / metabolism
  • Glucose
  • Glycosylation
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • 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

Substances

  • Fluorescent Dyes
  • Receptors, Mitogen
  • Rhodamines
  • Serum Albumin
  • Galactosamine
  • Glucose
  • Glucosamine