In vitro cytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2.

Antibodies conjugated to radionuclides emitting low-energy 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-HER-2 antibodies conjugated to (111)In, using the chelator benzyl-diethylenetriaminepentaacetic acid, or (125)I. Target cells were the breast carcinoma SK-BR-3 and the ovarian carcinoma SK-OV-3.

177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo.

Antibodies (Abs) conjugated to 177Lu, a relatively low-energy beta-particle emitter, were evaluated in vitro for their cytotoxic activity and in vivo for their therapeutic activity against disseminated B-cell lymphoma xenografts in SCID mice. 177Lu was compared with other beta-particle emitters ((131)I and 90Y), and also with emitters of low-energy electrons (LEEs, meaning Auger and conversion electrons of < 50 keV). The Abs used reacted with CD20, CD74 or HLA-DR, and the target cell was the Raji B lymphoma.

Therapy of small subcutaneous B-lymphoma xenografts with antibodies conjugated to radionuclides emitting low-energy electrons.

Purpose: Radionuclides emitting low-energy electrons (Auger and conversion electrons of <50 keV) are potentially useful for cancer therapy when conjugated to an antibody, because they can irradiate the cell to which they bind while producing relatively little irradiation of surrounding cells and tissues. We showed previously the ability of such antibody conjugates to treat micrometastatic, disseminated human B-lymphoma in a severe combined immunodeficient mouse model using an anti-CD74 antibody. In this study, we have evaluated the ability of such conjugates to treat s.

In vitro toxicity of A-431 carcinoma cells with antibodies to epidermal growth factor receptor and epithelial glycoprotein-1 conjugated to radionuclides emitting low-energy electrons.

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.

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.