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

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.