Use of galactosylated-streptavidin as a clearing agent with 111In-labeled, biotinylated antibodies to enhance tumor/non-tumor localization ratios.
Optimal tumor imaging using radiolabeled antibodies (Abs) depends on obtaining the highest possible tumor/non-tumor localization ratios. To increase this ratio, in a mouse xenograft model system, we induced rapid blood clearance of the Ab after extensive penetration of a solid tumor, at 24 hr after Ab injection. By using galactosylated streptavidin (gal-SA) as a clearing agent for biotinylated Abs, and by using an 111In-DTPA (diethylenetriaminepentaacetic acid) label, clearance was directed to hepatocytes (as opposed to Kupffer cells), and the radiolabel was excreted by the hepatocytes into bile, thereby reducing accumulation in the liver. In this study, we directly compared this approach with the use of 99mTc-F(ab)2 fragments, using the same Ab to carcinoembryonic antigen (CEA), with a colon carcinoma xenograft. The gal-SA clearance method produced substantially higher tumor/non-tumor localization ratios for all tissues except the liver, and even for the liver the disadvantage of the gal-SA clearance method was small. We also tested the gal-SA clearance method with a xenograft model of human B-cell lymphoma, using anti-CD22. High tumor/non-tumor ratios were obtained, as previously described with carcinomas of the lung and colon. Therefore, this approach appears to be a generally applicable strategy to obtain relatively high tumor/non-tumor ratios.
Govindan
Serengulam V
SV
Immunomedics, Inc., Morris Plains, New Jersey, USA.
Griffiths
Gary L
GL
Michel
Rosana B
RB
Andrews
Philip M
PM
Goldenberg
David M
DM
Mattes
M Jules
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D019921:Biotinylation; D002272:Carcinoembryonic Antigen / Q000276:immunology; D015815:Cell Adhesion Molecules; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007205:Indium Radioisotopes; D037102:Lectins / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging* / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D004369:Pentetic Acid; D016719:Radioimmunodetection; D051918:Sialic Acid Binding Ig-like Lectin 2; D019809:Streptavidin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D002272:Carcinoembryonic Antigen; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D004369:Pentetic Acid; D019809:Streptavidin