Peptide conjugates for EGFR-targeting

We have synthesized ⁶⁴Cu-labelled peptide conjugates based on a 1,4,7-triazacyclononane (TACN) framework that may be applied for in vivo PET imaging. A peptide sequence (LARLLT, “D4”) was used to target the epidermal growth factor receptor (EGFR). Overexpression and mutations of this cell-surface receptor are involved in carcinogenesis and progression of many human cancers.

Four different linker groups were introduced to influence solubility and lipophilicity. The TACN-peptide conjugates are obtained in high yields after purification by RP-HPLC. Radiolabelling with ⁶⁴Cu(II) was rapidly achieved under mild conditions (pH = 5.5; 22 °C). The receptor binding abilities of the labelled conjugates have been evaluated using immunoprecipitation and by determination of the dissociation constants, revealing only weak interactions (K_d > 100 nM) compared to its native ligand epidermal growth factor (EGF; K_d = 0.04 ± 0.002 nM). However, it was not determined if the “D4” peptide alone could target the EGFR.