68 Ga-labelled NOTA-RGD-GE11 peptide for dual integrin and EGFR-targeted tumour imaging.

INTRODUCTION: Multiple peptide receptors are co-expressed in many types of cancers. Arg-Gly-Asp (RGD) and GE11 peptides specifically target integrin αV β3 and EGFR, respectively. Recently, we designed and synthesized a heterodimer peptide NOTA-c(RGDyK)-GE11 (NOTA-RGD-GE11). The aim of this study was to investigate the characteristics of NOTA-RGD-GE11 for dual receptor imaging.

METHODS: NOTA-RGD-GE11 heterodimer was labelled with 68 Ga. The dual receptor binding affinity was investigated by antibody competition binding assay. The in vitro and in vivo characteristics of [68 Ga]Ga-NOTA-RGD-GE11 were investigated and compared with that of monomeric peptides [68 Ga]Ga-NOTA-RGD and [68 Ga]Ga-NOTA-GE11.

RESULTS: NOTA-RGD-GE11 had binding affinities with both integrin αV β3 and EGFR. The dual receptor targeting property of [68 Ga]Ga-NOTA-RGD-GE11 was validated by blocking studies in a NCI-H292 tumour model. [68 Ga]Ga-NOTA-RGD-GE11 showed higher tumour uptake than [68 Ga]Ga-NOTA-RGD and [68 Ga]Ga-NOTA-GE11 in biodistribution and PET/CT imaging studies.

CONCLUSION: The dual receptor targeting and enhanced tumour uptake of [68 Ga]Ga-NOTA-RGD-GE11 warrant its further investigation for dual integrin αV β3 and EGFR-targeted tumour imaging.