68Ga-NOTA-RGD-GE11

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 68Ga and purified using reversed‐phase high‐performance liquid chromatography. The 68Ga‐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.