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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

Center for Molecular Medicine and Immunology, Belleville, New Jersey

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 ß-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: With conjugates of ¹¹¹In, very potent killing was obtained with both of the Abs, with 100% kill (approximately 4–5 logs) even at subsaturating Ab concentrations. Lower levels of kill were obtained with ¹²⁵I or ¹³¹I conjugates. Conjugates with ¹³¹I, a ß-particle emitter, produced greater nonspecific toxicity. The greater potency of ¹¹¹In could be attributed to the higher specific activity that was obtained routinely with this radiolabel, up to 70 mCi/mg. Uptake of radioactivity peaked at approximately 200 cpm per cell. Dosimetry calculations, using subcellular S values, demonstrated that the toxicity observed was consistent with the amount of radiation delivered to the nucleus.

Conclusions: These results are similar to previous results obtained with B lymphoma cells and indicate that this approach is applicable to a wide range of tumor types. Radionuclides emitting low-energy electrons are effective at killing target cells with relatively little nonspecific toxicity, if sufficient activity is delivered to the cell. Most Abs to high-density cell surface antigens would probably be effective.

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