Development and biological evaluation of 68 Ga-labeled peptides for potential application in HER2-positive colorectal cancer.

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 [ ⁶⁸ Ga]Ga-ES-01 and [ ⁶⁸ Ga]Ga-ES-02. The results show that [ ⁶⁸ Ga]Ga-ES-01 and [ ⁶⁸ Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [ ⁶⁸ Ga]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 [ ⁶⁸ Ga]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 ⁶⁸ Ga-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 [ ⁶⁸ Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [ ⁶⁸ Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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