Differences in biodistribution of the anti-(carcinoembryonic antigen) murine monoclonal antibody CE-25, its F(ab')2 fragment and its intact mainly human chimeric form CE 4-8-13. Dependence on tumour size and amount of antibody injected

Cancer Immunol Immunother. 1994 Dec;39(6):375-82. doi: 10.1007/BF01534424.

Abstract

The effect of the size of the tumour and the amount of antibody injected on the biodistribution of a family of radioiodinated antibodies was studied. The intact mouse anti-(carcinoembryonic antigen) (anti-CEA) monoclonal antibody CE-25, its F(ab')2 fragment and the intact human-mouse chimeric from CE 4-8-13 were evaluated in a model system using the human CEA-producing colon xenograft T 380 grown in nude mice. The relative retention (the percentage of the injected dose per gram of tissue), of mouse mAb and F(ab')2 in tumour and most normal tissues 1 day after injection was independent of the antibody dose; after 4 days the mAb values increased with increasing antibody dose. The relative retention of chimeric mAb increased with increasing antibody dose 1 day after injection and also slightly after 4 days. The relative retention in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from day 1 to day 4; for chimeric mAb this value decreased. In normal tissues the relative retention of mouse mAb decreased from day 1 to day 4, but the relative retention of chimeric mAb in normal tissue dropped rapidly and changed little afterwards. Thus the biokinetics of antibodies is "species"-dependent: foreign, mainly human, chimeric antibody clears faster from normal mouse tissue than mouse antibody and reaches lower concentrations.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Carcinoembryonic Antigen / immunology*
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / metabolism*
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Radioimmunodetection
  • Radioimmunotherapy
  • Recombinant Fusion Proteins / metabolism*
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Immunoglobulin Fab Fragments
  • Recombinant Fusion Proteins