Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Bioorg Chem. 2024 Oct;151:107645. doi: 10.1016/j.bioorg.2024.107645. Epub 2024 Jul 15.
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 [Ga]Ga-ES-01 and [Ga]Ga-ES-02. The results show that [Ga]Ga-ES-01 and [Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [Ga]Ga-ES-02 demonstrated higher binding affinity (K = 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 [Ga]Ga-ES-02 (SUV = 0.87 ± 0.03; SUV = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 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 [Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.
结直肠癌（CRC）是世界上最致命和最常见的恶性肿瘤之一。人表皮生长因子受体 2（HER2）是诊断和治疗 CRC 的有前途的靶点。在这项研究中，我们旨在设计、合成和标记针对 HER2 阳性 CRC 的基于肽的正电子发射断层扫描（PET）示踪剂，即 [Ga]Ga-ES-01 和 [Ga]Ga-ES-02。结果表明，[Ga]Ga-ES-01 和 [Ga]Ga-ES-02 具有亲水性、快速的药代动力学特性和优异的稳定性。[Ga]Ga-ES-02 对 CRC 中的 HER2 表现出更高的结合亲和力（K = 24.29 ± 4.95 nM）。在 HER2 阳性 HT-29 CRC 异种移植小鼠模型中，注射 [Ga]Ga-ES-02 后 PET 研究显示出特异性肿瘤摄取（SUV = 0.87 ± 0.03；SUV = 0.64 ± 0.02）。在生物分布研究中，注射后 30 分钟 Ga-ES-02 的 T/M 比值达到最大值 4.07 ± 0.34。总之，我们成功合成并评估了两种新型基于肽的 PET 示踪剂。我们的数据表明，[Ga]Ga-ES-01/02 能够靶向 HER2 阳性结直肠癌，其中 [Ga]Ga-ES-02 具有更好的成像效果、增强的靶向性和更高的特异性。
