Amplified delivery of indium-111 to EGFR-positive human breast cancer cells

A method is described to amplify the delivery of In-111 to human breast can cer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) biocon jugate substituted preferentially in the HSA domain with multiple DTPA meta l chelators for In-111. In-111-DTPA-HSA-hEGF exhibited a lower receptor-bin ding affinity than In-111-DTPA-hEGF but was rapidly and specifically bound, internalized and translocated to the nucleus in EGFR-positive MDA-MB-468 b reast cancer cells. In-111-DTPA-HSA-hEGF was cytotoxic in vitro mainly thro ugh the emission of short-range Auger electrons and partially through the e ffects of the hEGF moiety to MDA-MB-468 cells overexpressing EGFR (1-2 x 10 (6) receptors/cell) but not towards MCF-7 breast cancer cells with a 100-fo ld lower level of EGFR on their surface. The cytotoxicity in vitro against MDA-MB-468 cells of In-111-DTPA-HSA-hEGF substituted with nine DTPA chelato rs was enhanced 4-fold compared to In-111-DTPA-hEGF monosubstituted with DT PA. Studies are planned to further evaluate In-111-DTPA-HSA-hEGF in vivo as a new imaging and targeted radiotherapeutic agent for breast cancer. (C) 2 001 Elsevier Science Inc. All rights reserved.