title: Synthesis of (68)Ga-labeled NOTA-RGD-GE11 heterodimeric peptide for dual integrin and epidermal growth factor receptor-targeted tumor imaging.
abstract: Radiolabeled Arg-Gly-Asp (RGD) peptide analogs have been extensively studied for αvβ3 integrin-targeted angiogenesis imaging. According to recently presented evidence, the dodecapeptide GE11 has high affinity to the epidermal growth factor receptor (EGFR), which is overexpressed in many types of cancer. Dual-receptor molecular imaging probes with two different heterodimeric peptides exhibit improved cancer targeting efficacy. In the present study, the design and synthesis of a new RGD-GE11 peptide heterodimer for dual αvβ3 integrin/EGFR-targeted cancer imaging are described. The RGD-GE11 heterodimer was linked with 6-aminohexanoic acid (6-Ahx) and cysteine and conjugated with 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA) to form NOTA-RGD-cys-6-Ahx-GE11. The monomeric peptides, NOTA-cys-6-Ahx-GE11 and c(RGDyK), were formed by a peptide synthesizer. The peptide heterodimer NOTA-RGD-GE11 was obtained by NOTA-cys-6-Ahx-GE11 and maleimidopropyl-c(RGDyK) conjugation with a thioether linkage. The NOTA peptide conjugate was labeled with freshly eluted (68)Ga and purified using reversed-phase high-performance liquid chromatography. The (68)Ga-NOTA-RGD-cys-6-Ahx-GE11 was successfully prepared, in this study, with a radiochemical yield of 85% and a radiochemical purity of >98%. These results warrant further investigation of this heterodimeric peptide's binding affinity to the receptors.
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Longtan District, Taoyuan City, Taiwan.
authors.forename: Hung-Man
authors.initials: HM
authors.lastname: Yu
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Longtan District, Taoyuan City, Taiwan.|Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Jyun-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Longtan District, Taoyuan City, Taiwan.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Lin
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Longtan District, Taoyuan City, Taiwan.
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
mesh_terms: D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: C584295:68Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-Tyr-Lys); C000606135:68Ga-NOTA-RGD-GE11; D056831:Coordination Complexes; C572557:GE11 peptide; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D004815:Epidermal Growth Factor
keywords: GE11; Ga-68; RGD; epidermal growth factor receptor (EGFR); heterodimer peptide; integrin αvβ3; positron emission tomography (PET)