BINDING, INTERNALIZATION AND DEGRADATION OF EGF-DEXTRAN CONJUGATES IN2 HUMAN BLADDER-CANCER CELL-LINES

Bladder carcinomas often have an increased number of epidermal growth factor (EGF) receptors. The EGF receptors can, in these cases, be targ ets for toxic conjugates. In this study, EGF-dextran conjugates were u sed as targeting agents with therapeutic potential. The binding, inter nalization and degradation of I-125-EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines, were investigated. The beh aviour of I-125-EGF was studied as a comparison. The I-125-EGF-dextran showed a continuous increase in binding up to 24 hr, while I-125-ECF exhibited maximum binding after about 90 min. Both cell lines showed s imilar binding patterns. The binding of I-125-EGF-dextran and I-125-EG F was, on both cell lines, receptor-specific since the binding could b e displaced with non-radioactive EGF. Analysis of internalized and mem brane-bound I-125 activity after administration of I-125-ECF-dextran s howed that most of the activity was membrane-bound. A large part of bo th the internalized and the membrane-bound activity remained cell-asso ciated up to 24 hr. The internalized and membrane-bound activity after administration of I-125-EGF decreased rapidly and only a small fracti on remained cell-associated after 24 hr. I-125-EGF-dextran remained ce ll-associated, with only a limited release of low- and high-molecular- weight radioactivity throughout the 24-hr period, while I-125-EGF was extensively degraded and released into the incubation medium as low-mo lecular-weight radioactivity during this time. Several qualities of th e I-125-EGF-dextran conjugates might be favourable for targeted radiot herapy. (C) 1997 Wiley-Liss, Inc.