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

  • Nucl Med Biol. 2019 Jan-Feb:68-69:22-30. doi: 10.1016/j.nucmedbio.2018.11.003.
Chien-Jen Chen  1 ,  Chen-Hsin Chan  1 ,  Kun-Liang Lin  1 ,  Jyun-Hong Chen  1 ,  Chun-Hao Tseng  1 ,  Ping-Yen Wang  1 ,  Chuan-Yi Chien  1 ,  Hung-Man Yu  2 ,  Wuu-Jyh Lin  3
Affiliations
  • 1. Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan City, Taiwan, ROC.
  • 2. Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan City, Taiwan, ROC. Electronic address: [email protected].
  • 3. Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan City, Taiwan, ROC. Electronic address: [email protected].
PMID: 30578136 DOI: 10.1016/j.nucmedbio.2018.11.003
Abstract

Introduction: Multiple peptide receptors are co-expressed in many types of cancers. Arg-Gly-Asp (RGD) and GE11 peptides specifically target Integrin αVβ3 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 68Ga. The dual receptor binding affinity was investigated by antibody competition binding assay. The in vitro and in vivo characteristics of [68Ga]Ga-NOTA-RGD-GE11 were investigated and compared with that of monomeric peptides [68Ga]Ga-NOTA-RGD and [68Ga]Ga-NOTA-GE11.

Results: NOTA-RGD-GE11 had binding affinities with both Integrin αVβ3 and EGFR. The dual receptor targeting property of [68Ga]Ga-NOTA-RGD-GE11 was validated by blocking studies in a NCI-H292 tumour model. [68Ga]Ga-NOTA-RGD-GE11 showed higher tumour uptake than [68Ga]Ga-NOTA-RGD and [68Ga]Ga-NOTA-GE11 in biodistribution and PET/CT imaging studies.

Conclusion: The dual receptor targeting and enhanced tumour uptake of [68Ga]Ga-NOTA-RGD-GE11 warrant its further investigation for dual Integrin αVβ3 and EGFR-targeted tumour imaging.

Keywords
EGFR; Ga-68; Heterodimer peptide; Integrin α(V)β(3); PET imaging.
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