title: 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.
authors.affiliation: Department of Internal Medicine, University of California, Davis.
authors.forename: S V
authors.initials: SV
authors.lastname: Deshpande
authors.forename: R
authors.initials: R
authors.lastname: Subramanian
authors.forename: M J
authors.initials: MJ
authors.lastname: McCall
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
authors.forename: C F
authors.initials: CF
authors.lastname: Meares
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes; D004355:Drug Stability; D004492:Edetic Acid / Q000378:metabolism / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008099:Liver / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000378:metabolism*; D004369:Pentetic Acid / Q000378:metabolism / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C063369:indium 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid; C054343:1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid; D004369:Pentetic Acid; D004492:Edetic Acid