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

• Published in: Bioconjugate chemistry Vol. 2; no. 6; pp. 415 - 421
• Main Authors: Smith-Jones, Peter M, Fridrich, Raimund, Kaden, Thomas A, Novak-Hofer, Ilse, Siebold, Karl, Tschudin, Daniel, Maecke, Helmut R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-11-1991
• Subjects: 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
• DOI: 10.1021/bc00012a006
• EISSN: 1520-4812
• ISSN: 1043-1802

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.