Lin Yizi, Lin Yi, Lin Xiao, Sun Xiaotian, Luo Kun
Department of Radiology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
J Cancer. 2019 Jun 9;10(15):3420-3426. doi: 10.7150/jca.31087. eCollection 2019.
Precision medicine is emphasizing not only at individual but also at disease molecule level in modern medicine. Therefore, target-specific molecular agents are crucial for precise diagnosis and treatment. We developed a peptide agent that binds a critical chemokine receptor-CXCR4 and could be used to detect tumor status. Confocal images showed binding of the peptide agent to human osteosarcoma cells. Clinical gold-standard molecular imaging agent PET showed tumors had high glucose metabolism, CT showed that these xenograft tumors were calcified and displayed hypervascularity. Peptide imaging demonstrated that these tumors were CXCR4 positive. However, Western blot protein analysis revealed a discordance between the tumor and the CXCR4 targeted agent, suggesting that small changes in peptide sequences have profound effect on binding to their targets. We also demonstrated the molecular screening by modifying the peptide sequence and thereby altering the binding properties of the agent. In conclusion, this study demonstrates that small molecule peptide agents can be used as an additional diagnostic tool for precision medicine.
精准医学在现代医学中不仅强调个体水平，还强调疾病分子水平。因此，针对特定靶点的分子药物对于精确诊断和治疗至关重要。我们开发了一种能结合关键趋化因子受体CXCR4的肽类药物，可用于检测肿瘤状态。共聚焦图像显示该肽类药物与人骨肉瘤细胞结合。临床金标准分子成像药物PET显示肿瘤具有高糖代谢，CT显示这些异种移植肿瘤发生钙化并表现出血管增多。肽成像显示这些肿瘤为CXCR4阳性。然而，蛋白质免疫印迹分析显示肿瘤与CXCR4靶向药物之间存在不一致，表明肽序列的微小变化对其与靶点的结合有深远影响。我们还通过修饰肽序列展示了分子筛选，从而改变了药物的结合特性。总之，本研究表明小分子肽类药物可作为精准医学的一种额外诊断工具。
