131I-IMP-R4-hRS7 is a promising new agent for RAIT, providing significant therapeutic advantage in comparison to the conventionally 131I-labeled antibody.
Purpose: The ability of antibodies (Abs) conjugated to radionuclides emitting low-energy electrons to specifically kill nonadherent lymphoma target cells in vitro was demonstrated previously. This study extends this work to adherent carcinoma cells. The fact that these cells are spread out on plastic can potentially make it more difficult to deliver radiation to the nucleus from decays in the cytoplasm or on the cell surface.Experimental Design: The Abs tested were anti-epidermal growth factor receptor and anti-epithelial glycoprotein-1, conjugated to indium-111 or iodine-125, which emit low-energy Auger and conversion electrons. Conjugates of the -particle emitter, iodine-131, also were tested, for comparison. Abs were incubated with the cells for 2 days, and then the treated cells were assayed for colony-forming units. The radiation dose delivered to the nucleus was calculated from the cumulative decays per cell.Results
Antibodies conjugated to radionuclides emitting lowenergy electrons, which include Auger electrons and some conversion electrons, were recently shown to efficiently kill cells bearing a high density of the antigen recognized. The primary purpose of this study was to determine if such killing could be obtained with anti -
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.