Hyaluronidase-induced periodic modulation of the interstitial fluid pressure increases selective antibody uptake in human osteosarcoma xenografts

Anticancer Res. Sep-Oct 2000;20(5B):3513-9.

Abstract

Periodic modulation of the elevated interstitial fluid pressure might improve filtration and uptake of tumor-targeting macromolecules (e.g. radioimmunoconjugates) in solid tumors. Cycling of the tumor interstitial fluid pressure was initiated by intratumoral injections of bovine testicular hyaluronidase (BTH, 1,600 U) in osteosarcoma-bearing nude mice. BTH injection was repeated at 3-day intervals up to 9 days, in conjunction with tail vein injections of 125I-labeled TP-3 monoclonal antibody against an osteosarcoma-associated antigen (n = 9) or non-specific 125I-labeled UPC-10 antibody (n = 9). Control mice received intratumoral injections of phosphate buffered saline (n = 18). The radioactivities of tumor and normal tissues (blood, liver, kidney and spleen) were measured and compared between the different groups. BTH injections increased the tumor uptake of specific 125I-labeled TP-3 significantly by approximately 70% in mice receiving 3 fractions compared to 1-2 fractions of the antibody (p < 0.05). The tumor/normal tissue ratio in mice receiving 3 fractions of 125I-labeled TP-3 (n = 5) was significantly higher for all tissues, compared with mice receiving 1-2 fractions (n = 4) (p < 0.05). Control injections did not affect the tumor/blood ratio, but increased the uptake of 125I-labeled TP-3 significantly in kidney and spleen (p < 0.05). Also, BTH reduced the uptake of 125I-labeled UPC-10 in tumor and liver by approximately 20% compared with controls (p < 0.05). The results indicate that periodic lowering of the tumor interstitial fluid pressure might increase the specificity of blood-borne monoclonal antibodies to solid tumors in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibody Specificity
  • Autoradiography
  • Cattle
  • Epitopes / biosynthesis
  • Epitopes / immunology
  • Extracellular Space / drug effects*
  • Extracellular Space / metabolism
  • Extracellular Space / physiology
  • Female
  • Flow Cytometry
  • Humans
  • Hyaluronoglucosaminidase / pharmacology*
  • Immunoconjugates / blood
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacokinetics
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Injections, Intralesional
  • Iodine Radioisotopes / blood
  • Iodine Radioisotopes / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Osteosarcoma / immunology*
  • Osteosarcoma / metabolism
  • Osteosarcoma / physiopathology
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • Immunoconjugates
  • Immunoglobulin G
  • Iodine Radioisotopes
  • Hyaluronoglucosaminidase