IN-VIVO EVALUATION OF EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR DENSITY ON HUMAN TUMOR XENOGRAFTS USING RADIOLABELED EGF AND ANTI-(EGF RECEPTOR) MAB-425

In order to study the potential of non-invasive scintigraphic evaluati on of the epidermal growth factor (EGF) receptor status in vivo, the b iokinetics and tumor binding of I-125-EGF and anti-(EGF receptor) mAb 425 were investigated in nude mice bearing human tumor xenografts with different EGF-receptor densities as determined by a radioreceptor ass ay. The results demonstrated a tumor uptake for both substances depend ing on the receptor level. The EGF receptor status, however, was refle cted slightly better by the binding of EGF to tumor tissue compared to the mAb. The rapid blood clearance of EGF with a plasma half-life of less than I min led to a tumor-to-blood ratio of approximately 3 withi n 6 h after injection in tumors with a high receptor expression. A sim ilar ratio for the mAb was not obtained before day 6 after injection. The absolute concentration of EGF, however, was low compared to the mA b. Therefore, it can be concluded that the EGF receptor status as a ta rget for (radio)immunotherapy can be evaluated in vivo with EGF labele d with a short-life positron-emitting radionuclide or with monoclonal antibodies to the EGF receptor or their fragments.