Effect of different linkages between chelates and monoclonal antibodies on levels of radioactivity in the liver.
After injection of radiometal labeled antibodies, the radionuclide accumulates in the liver. This might be altered by a metabolizable linkage between metal chelate and antibody. Four benzyl-EDTA chelating agents were synthesized and conjugated to mouse monoclonal antibody Lym-1. Liver uptake of 111In in nontumored mice 72 h after injection was 2.2, 13.4, 7.6 and 20% for disulfide, thioether, thiourea or peptide linkages, respectively. 111In excreted in the urine was still in the benzyl-EDTA chelate form, as shown by binding to a specific anti-chelate antibody.
Deshpande
S V
SV
Department of Internal Medicine, University of California, Davis, Medical Center, Sacramento 95817.
Denardo
S J
SJ
Meares
C F
CF
McCall
M J
MJ
Adams
G P
GP
Denardo
G L
GL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002614:Chelating Agents / Q000138:chemical synthesis; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007205:Indium Radioisotopes