Metabolism of indium-111-labeled murine monoclonal antibody in tumor and normal tissue of the athymic mouse.
We have studied the fate of radiometal metabolism in vivo by analyzing the molecular form of radiolabeled anti-carcinoembryonic antigen (CEA) in tissues. Athymic mice bearing colonic tumor xenografts were injected i.v. with 111In-isothiocyanate-benzyl-DTPA-(SCN-Bz-DTPA) IgG or 111In-(SCN-Bz-DTPA) F(ab')2, and then killed daily for up to four days. Liver, kidney, and tumor were extracted and the supernatants, plasma and urine samples were analyzed by HPLC, ITLC, HPIEC and SDS-PAGE. By HPLC, the activity in normal tissue and tumor was associated principally with two major components. The first was native MAb and the second was a low molecular weight component (LMWF). On Day 1, the native-sized IgG was the predominant form (greater than 65%), but progressively decreased to less than 20% by Day 4. For the F(ab')2, even by Day 1 approximately 90% of the activity was associated with the LMWF. This LMWF was resolved further by HPIEC and SDS-PAGE into several metabolites that appear to be 111In-SCN-Bz-DTPA and 111In-SCN-Bz-DTPA bound to peptide fragments.
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
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C
Motta-Hennessy
R M
RM
Sharkey
D M
DM
Goldenberg
D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes; C054343:1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid; D004369:Pentetic Acid