Contrast-enhanced computed tomography combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor and vascular endothelial growth factor receptor in the screening of early esophageal cancer

增强 CT 扫描联合壳聚糖-Fe3O4 纳米粒子靶向成纤维细胞生长因子受体和血管内皮生长因子受体在早期食管癌筛查中的应用

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作者:Juanjuan Gai, Zhenli Gao, Liqiang Song, Yongyun Xu, Weixin Liu, Chuanxin Zhao

Abstract

Esophageal cancer is a malignant tumor with a relatively high invasiveness, metastatic potential and worldwide incidence among human cancers. The majority of patients with esophageal cancer are diagnosed in a late tumor stage due to a lack of advanced and sensitive protocols for the diagnosis of patients with early-stage esophageal cancer. In the current study, contrast-enhanced computerized tomography (CECT) combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR; CECT-CNFV) were used to diagnose patients with suspected esophageal cancer. A Chitosan-Fe3O4-parceled bispecific antibody targeting FGFR and VEGFR was produced and its affinity to esophageal cancer cells was determined both in vitro and in vivo. A total of 320 patients with suspected esophageal cancer were voluntarily recruited to evaluate the efficacy of CECT-CNFV in the diagnosis of early-stage esophageal cancer. All participants were subjected to CT and CECT-CNFV to detect whether tumors were present in the esophageal area. A Chitosan-Fe3O4 nanoparticles contrast agent was orally administered at 20 min prior to CT and CECT-CNFV. The results demonstrated that CECT-CNFV improved diagnostic sensitivity and provided a novel protocol for the diagnosis of tumors in patients with suspected gastric cancer at an early-stage. Furthermore, the resolution ratio of images was enhanced by CECT-CNFV, which enabled the visualization of tiny tumor nodules in esophageal tissue. Clinical data demonstrated that CECT-CNFV diagnosed 200 patients with suspected early-stage esophageal cancer and 120 patients as tumor free. In addition, CECT-CNFV exhibited higher signal enhancement of tumor nodules than CT, suggesting a higher accuracy and accumulation of nanoparticle contrast agent within the tumor nodules of esophageal tissue. Notably, the survival rate of patients with esophageal cancer diagnosed at an early-stage by CECT-CNFV was higher than the mean five-year survival rate (P<0.01). In conclusion, CECT-CNFV enhanced the sensitivity and accuracy of CT in the diagnosis of early-stage esophageal cancer. Thus, CECT-CNFV may improve the accuracy of CT in the diagnosis of mural enhancement in patients with esophageal cancer.

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