Introduction of five potentially metabolizable linking groups between 111In-cyclohexyl EDTA derivatives and F(ab')2 fragments of anti-carcinoembryonic antigen antibody--II. Comparative pharmacokinetics and biodistribution in human colorectal carcinoma-bearing nude mice

Nucl Med Biol. 1993 Aug;20(6):763-71. doi: 10.1016/0969-8051(93)90163-o.

Abstract

The five linker-containing immunoconjugates described in the preceding paper were labeled with 111In and tested for their biodistribution, pharmacokinetics and immunoscintigraphic imaging properties in tumor-xenografted nude mice. The results were compared with DTPADA and CDTAMA for reference. Results showed that, for immunoscintigraphy, the derivatives in decreasing order of effectiveness were: aliphatic (tumor/liver > 4.5 and tumor/kidney > 6.5 at 96 h), thioether (tumor/liver > 3 and tumor/kidney > 1.2 at 24 h), ethylene glycol succinate (tumor/liver > 1.7 and tumor/kidney > 0.5 at 24 h) and disulfide (tumor/liver > 0.5 and tumor/kidney > 0.6 at 96 h). Pharmacokinetic results were complementary with those of the biodistribution studies and provide a basis for the study of in vivo metabolic mechanisms of linker-immunoconjugates. Indium-111-labeled linker-immunoconjugates appear promising for tumor imaging with better contrast than what is obtained with the use of the conventional 111In-DTPA dianhydride chelate.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / metabolism*
  • Animals
  • Antibodies / metabolism*
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / metabolism
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / metabolism*
  • Cross-Linking Reagents / pharmacokinetics*
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / pharmacokinetics
  • Female
  • Humans
  • Indium Radioisotopes / pharmacokinetics*
  • Liver / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Radionuclide Imaging
  • Tissue Distribution

Substances

  • Antibodies
  • Carcinoembryonic Antigen
  • Cross-Linking Reagents
  • Indium Radioisotopes
  • CDTA
  • Edetic Acid