title: Avidin targeting of intraperitoneal tumor xenografts.
abstract: BACKGROUND
  Lectins (proteins that bind specific sugar molecules on glycoproteins and glycolipids) are expressed at various levels on the surface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors. Avidin (a highly glycosylated, positively charged protein found in egg white) contains terminal N-acetylglucosamine and mannose residues that bind to some lectins. In this study, we tested the ability of avidin, labeled through conjugation to radioactive biotin (a B vitamin), to target intraperitoneal tumors.
  
  
  METHODS
  Biotin was radioactively labeled with 111In. Four tumor models (one ovarian, one lung, and two colon) were established in nude mice by intraperitoneal injection of cultured cancer cells. The following two approaches were used in the intraperitoneal administration of avidin: 1) radioactive biotin-avidin conjugates were injected and 2) avidin was injected 1-24 hours before the injection of radioactive biotin (avidin pretargeting; avidin-biotin conjugates formed in vivo). The distribution of injected radioactivity in the tissues of treated animals was assessed.
  
  
  RESULTS
  Radiolabeled avidin localized highly and rapidly in the tumors. More than 50% of the administered dose of avidin-biotin conjugate accumulated per gram of tumor tissue 2 hours after injection; high tumor uptake of radioactivity was observed up to 24 hours after conjugate injection. In contrast, accumulation of radioactivity in normal tissues was low, yielding high tumor to nontumor ratios. With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased.
  
  
  CONCLUSIONS
  Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.
authors.affiliation: Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan. yao@kuhp.kyoto-u.ac.jp
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Sakahara
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: Y
authors.initials: Y
authors.lastname: Arano
authors.forename: J
authors.initials: J
authors.lastname: Konishi
mesh_terms: D000818:Animals; D001360:Avidin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D007205:Indium Radioisotopes; D001360:Avidin