A NEW RADIOLIGAND FOR THE EPIDERMAL GROWTH-FACTOR RECEPTOR - IN-111 LABELED HUMAN EPIDERMAL GROWTH-FACTOR DERIVATIZED WITH A BIFUNCTIONAL METAL-CHELATING PEPTIDE

More specific radiopharmaceuticals are currently being evaluated for t he in vivo detection and therapy of breast cancer. The human epidermal growth factor (hEGF) represents a good radiopharmaceutical candidate in view of the reported overexpression of its receptor by breast cance r cells. To enhance the imaging potential of this peptide ligand, a sy nthetic strategy was developed to rapidly create small peptides contai ning a large number of metal-chelating groups that can be readily coup led to hEGF. A prototypic 15-amino acid branched peptide containing fo ur EDTA-like chelator groups was assembled by solid phase peptide synt hesis. The metal chelating peptide, abbreviated MCP-4-EDTA-SH, was sel ectively incorporated into hEGF(1-51) at its unique N-terminus amino g roup. The coupling of a single MCP-4-EDTA-SH into hEGF(1-51) was confi rmed by SDS polyacrylamide gel electrophoresis, western blotting, and amino acid analysis. The protein conjugate was successfully labeled wi th In-111. Its specific binding to EGF receptors present on MDA-MB-468 breast cancer cells confirmed that such a construct retains the prope rties of the natural ligand.