Metabolism of indium chelates attached to monoclonal antibody: Minimal transchelation of indium from benzyl-EDTA chelate in vivo

The metabolism of radiolabeled antibodies is important for radioimmunoimaging and therapy. The loss of indium-111 (¹¹¹In) from the chelate can pose problems in imaging and increases the radiation dose to normal tissues. We have evaluated the loss in vivo of ¹¹¹In from Lym-1-benzyl-EDTA-¹¹¹In (an antibody conjugated with isothiocyanatobenzyl-EDTA) in normal mice. A monoclonal antibody (CHA 255) that binds to benzyl-EDTA-indium chelates, but not to other forms of indium, was used to measure the percent of ¹¹¹In remaining in the chelate. Four days after injection, 97.4 ± 2.2% of the ¹¹¹In in the liver was still in the benzyl-EDTA chelate, as was 99.4 ± 0.7% of the ¹¹¹In in the urine, and 99.1 ± 0.7% of the ¹¹¹In in the blood. Studies in vitro indicate that a benzyl-EDTA-¹¹¹In-antibody-chelate conjugate is more stable in human serum than a benzyl-DTPA-¹¹¹In conjugate, and that both benzyl-chelate conjugates are much more stable than an unsubstituted DTPA conjugate.