Antibody labeling with copper-67 using the bifunctional macrocycle 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid

Bioconjug Chem. 1991 Nov-Dec;2(6):415-21. doi: 10.1021/bc00012a006.

Abstract

The high kinetic stability of the Cu2+ complex of the chelator 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl]benzoic acid was demonstrated at physiological pH as well as under acidic conditions. The chelating agent was conjugated to AB35, a monoclonal antibody directed against CEA, without a significant loss of immunoreactivity. The conjugate could, under optimal labeling conditions, be labeled with 67Cu in acetate buffer with a full occupancy of ligands within 20 min. This radiolabeled conjugate showed no transfer of radiocopper to serum proteins in human serum over 7 days. The biodistribution in tumor-bearing mice was measured and compared to that of iodinated AB35. Tumor uptake was high with 15 +/- 3% ID (injected dose)/g after 24 h and 32 +/- 7% ID/g after 96 h for the 67Cu-labeled antibody and 13 +/- 4% ID/g after 24 h and 14 +/- 2% ID/g after 96 h for the 125I-labeled antibody. Whereas radioactivity in normal organs decreased with time after 24 h, increased residence time was shown up to 4 days with the 67Cu-labeled AB35.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / metabolism
  • Benzoates / chemistry
  • Binding Sites
  • Blood
  • Blood Proteins / metabolism
  • Carcinoembryonic Antigen / immunology*
  • Chelating Agents* / chemistry
  • Copper Radioisotopes*
  • Drug Stability
  • Heterocyclic Compounds / chemistry
  • Isotope Labeling*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / metabolism
  • Solutions
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Benzoates
  • Blood Proteins
  • Carcinoembryonic Antigen
  • Chelating Agents
  • Copper Radioisotopes
  • Heterocyclic Compounds
  • Solutions
  • 4-((1,4,8,11-tetraazacyclotetradec-1-yl)methyl)benzoic acid