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.
OBJECTIVE
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.


METHODS
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 beta-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 (111)In, 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 (125)I or (131)I conjugates. Conjugates with (131)I, a beta-particle emitter, produced greater nonspecific toxicity. The greater potency of (111)In 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.
Michel
Rosana B
RB
Center for Molecular Medicine and Immunology, Belleville, New Jersey, USA.
Castillo
Mary Ellen
ME
Andrews
Philip M
PM
Mattes
M Jules
MJ
D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000532:radiotherapy*; D002470:Cell Survival / Q000528:radiation effects*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007205:Indium Radioisotopes / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014846:Vulvar Neoplasms / Q000276:immunology / Q000532:radiotherapy*
D006023:Glycoproteins; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D066246:ErbB Receptors