Shao Huanyi, Lv Kaiji, Wang Pengfei, Jin Jinji, Cai Yiqi, Chen Jun, Kamara Saidu, Zhu Shanli, Zhu Guanbao, Zhang Lifang
Department of Pediatric Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, China.
Front Microbiol. 2024 Oct 9;15:1464088. doi: 10.3389/fmicb.2024.1464088. eCollection 2024.
Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (Z539, Z546, and Z919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled Z affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled Z affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of Z affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer.
胃肠道癌是一种常见的恶性肿瘤，在全球范围内发病率很高。尽管诊断和治疗策略不断改进，但胃肠道肿瘤的总体预后仍然很差。癌胚抗原（CEA）在各种类型的癌症中高表达，尤其是在胃肠道癌中，这使其成为治疗干预的潜在靶点。因此，CEA的表达可用作肿瘤存在的指标，选为分子成像诊断的靶点，并有效地用于胃肠道癌的靶向治疗。在本研究中，我们报告了针对CEA蛋白的亲合体分子（Z539、Z546和Z919）的筛选和表征。通过表面等离子体共振（SPR）、免疫荧光和免疫组织化学分析证实了它们与重组CEA蛋白和天然CEA蛋白结合的能力。此外，DyLight755标记的Z亲合体在注射后1小时在肿瘤部位积聚，并在4小时内持续增强。DyLight755标记的Z亲合体在携带CEA+异种移植物的小鼠中表现出高肿瘤靶向特异性，并具有用于肿瘤靶向成像的良好特性。总体而言，我们的结果表明Z亲合体作为检测胃肠道癌中CEA表达的荧光分子成像探针具有潜在用途。
