title: A new radioligand for the epidermal growth factor receptor: 111In labeled human epidermal growth factor derivatized with a bifunctional metal-chelating peptide.
abstract: 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.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Rémy
authors.forename: R M
authors.initials: RM
authors.lastname: Reilly
authors.forename: K
authors.initials: K
authors.lastname: Sheldon
authors.forename: J
authors.initials: J
authors.lastname: Gariépy
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001943:Breast Neoplasms; D002614:Chelating Agents / Q000737:chemistry* / Q000378:metabolism; D003432:Cross-Linking Reagents; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D002614:Chelating Agents; D003432:Cross-Linking Reagents; D007205:Indium Radioisotopes; C099030:MCP-4-EDTA-SH; D010455:Peptides; D004815:Epidermal Growth Factor; D004492:Edetic Acid; D066246:ErbB Receptors