A New Radioligand for the Epidermal Growth Factor Receptor: 111In-Labeled Human Epidermal Growth Factor Derivatized with a Bifunctional Metal-Chelating Peptide

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.