A new radioligand for the epidermal growth factor receptor: 111In labeled human epidermal growth factor derivatized...

More specific radiopharmaceuticals are currently being evaluated for the 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 cancer cells. To enhance the imaging potential of this peptide ligand, a synthetic strategy was developed to rapidly create small peptides containing a large number of metal-chelating groups that can be readily coupled to hEGF. A prototypic 15-amino acid branched peptide containing four EDTA-like chelator groups was assembled by solid phase peptide synthesis. The metal chelating peptide, abbreviated MCP-4-EDTA-SH, was selectively incorporated into hEGF(1-51) at its unique N-terminus amino group. The coupling of a single MCP-4-EDTA-SH into hEGF(1-51) was confirmed by SDS polyacrylamide gel electrophoresis, western blotting, and amino acid analysis. The protein conjugate was successfully labeled with 111In. Its specific binding to EGF receptors present on MDA-MB-468 breast cancer cells confirmed that such a construct retains the properties of the natural ligand.