Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd= 67 nM and onset of k = 0.136 min−1(7.35 min) were determined. Serum stability was measured with a half-life of T1/2= 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.
肝细胞癌（HCC）已成为全球癌症负担的主要贡献者。早期癌症检测和图像引导手术需要改进的方法。肽类具有小尺寸特性，能够克服递送障碍，实现高肿瘤浓度和深层穿透。我们采用噬菌体展示技术，针对纯化的EpCAM蛋白胞外域进行生物淘选，并使用IRDye800作为近红外荧光团。鉴定出12肽序列HPDMFTRTHSHN，并在体外通过HCC细胞验证了其与EpCAM的特异性结合。测定其结合亲和力为kd=67 nM，起始结合速率k=0.136 min⁻¹（7.35分钟）。血清稳定性测定显示半衰期T₁/₂=2.6小时。近红外荧光成像显示，注射后1.5小时人源HCC患者来源异种移植瘤体内摄取达到峰值。此外，该肽能够结合肝脏和肺部的局部及远处转移灶。肽的生物分布显示肿瘤摄取量显著高于其他器官。动物尸检未发现急性毒性迹象。人肝组织免疫荧光染色显示，与肝硬化、腺瘤及正常样本相比，该肽能特异性结合HCC组织。
肿瘤(癌症)患者之家