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

Abstract Introduction Multiple peptide receptors are co-rexpressed in many types of cancers. Arg-Gly-Asp (RGD) and GE11 peptides specifically target integrin α V β 3 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 antibodies competition binding assay. The in vitro and in vivo characteristics of [ 68 Ga]Ga-NOTA-RGD-GE11 was 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 α V β 3 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 α V β 3 and EGFR-targeted tumour imaging.