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

Abstract

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 isothiocyanato-benzyl-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.