[68Ga]Ga-ES-02

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [⁶⁸Ga]Ga-ES-01 and [⁶⁸Ga]Ga-ES-02. The results show that [⁶⁸Ga]Ga-ES-01 and [⁶⁸Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [⁶⁸Ga]Ga-ES-02 demonstrated higher binding affinity (K_d = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [⁶⁸Ga]Ga-ES-02 (SUV_{15min max} = 0.87 ± 0.03; SUV_{30min max} = 0.64 ± 0.02). In biodistribution study, the T/M ratios of ⁶⁸Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [⁶⁸Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [⁶⁸Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.