AVIDIN TARGETING OF INTRAPERITONEAL TUMOR XENOGRAFTS

Background: Lectins (proteins that bind specific sugar molecules on gl ycoproteins and glycolipids) are expressed at various levels on the su rface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors, Avi din (a highly glycosylated, positively charged protein found in egg wh ite) contains terminal N-acetylglucosamine and mannose residues that b ind to some lectins, In this study, we tested the ability of avidin, l abeled through conjugation to radioactive biotin (a B vitamin), to tar get intraperitoneal tumors. Methods: Biotin was radioactively labeled with In-111. 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 intraperi toneal administration of avidin: 1) radioactive biotin-avidin conjugat es were injected and 2) avidin was injected 1-24 hours before the inje ction of radioactive biotin (avidin pretargeting; avidin-biotin conjug ates formed in vivo), The distribution of injected radioactivity in th e tissues of treated animals was assessed, Results: Radiolabeled avidi n localized highly and rapidly in the tumors, More than 50% of the adm inistered dose of avidin-biotin conjugate accumulated per gram of tumo r tissue 2 hours after injection; high tumor uptake of radioactivity w as observed up to 24 hours after conjugate injection, In contrast, acc umulation of radioactivity in normal tissues was low, yielding high tu mor to nontumor ratios, With avidin pretargeting, accumulation of radi oactivity in the liver, kidney, and spleen was reduced to a greater ex tent than that in the tumor, and tumor to nontumor ratios were increas ed, Conclusions: Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.