Binding of EGF peptide and EGF receptor antibodies and its fragments in different tumor models

Binding of epidermal growth factor (EGF) to the EGF receptor is known to tr igger a number of biological responses in the target cells including EGF re ceptor phosphorylation and stimulation of DNA synthesis leading to cell pro liferation. Agents that bind to the EGF receptors could have a significant role in the therapy of tumors that express increased numbers of receptors b y blocking the stimulatory effect of EGF, Different monoclonal antibodies ( MAbs) directed to the EGF receptor have been generated that inhibit EGF bin ding and do not induce activation of the receptor tyrosine kinase, When the re is sufficient uptake these antibodies can be used for immunotherapy and, after labeling with an appropriate radionuclide, also for radioimmunothera py, For evaluation of a ligand as a therapeutic agent, it is necessary to i nvestigate its binding characteristics in tumor cells and experimental tumo rs in vivo. Because the effectiveness of the antitumor activity of the MAb is dependent upon the amount of receptors in the tissue and the penetration of the MAb into the tissue, the receptor density, biokinetics, and tumor d istribution of the MAb or its fragments were evaluated in different tumor m odels. The results of the experimental studies with tumor cell spheroids an d different xenotransplanted human tumors have shown that the uptake and di stribution in the tumor tissue is dependent on the molecular weight of the ligand, The correlation between the uptake of the substances and the recept or density is an indication for a noninvasive scintigraphic characterizatio n of human tumors using radiolabeled compounds with specific binding to the tumor receptor and for selection of an optimal therapeutic regimen or radi onuclide targeting of the tumor.