Antibody labeling with copper-67 using the bifunctional macrocycle 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid.
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.
Smith-Jones
P M
PM
Radiopharmacy Division, Paul Scherrer Institut, Wuerenlingen, Switzerland.
Fridrich
R
R
Kaden
T A
TA
Novak-Hofer
I
I
Siebold
K
K
Tschudin
D
D
Maecke
H R
HR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D001565:Benzoates / Q000737:chemistry; D001665:Binding Sites; D001769:Blood; D001798:Blood Proteins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002614:Chelating Agents / Q000737:chemistry; D003301:Copper Radioisotopes; D004355:Drug Stability; D006571:Heterocyclic Compounds / Q000737:chemistry; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D012996:Solutions; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D001565:Benzoates; D001798:Blood Proteins; D002272:Carcinoembryonic Antigen; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D012996:Solutions; C074011:4-((1,4,8,11-tetraazacyclotetradec-1-yl)methyl)benzoic acid