Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Jiangsu Institute of Nuclear Medicine, Wuxi, China.
Sci Rep. 2018 Dec 13;8(1):17832. doi: 10.1038/s41598-018-36238-x.
This study aimed to explore the application of two radiotracers (F-fluorodeoxyglucose (FDG) and F-fluoromisonidazole (FMISO)) in monitoring hepatic metastases of human colorectal cancer (CRC). Mouse models of CRC hepatic metastases were established by implantation of the human CRC cell lines LoVo and HT29 by intrasplenic injection. Wound healing and Transwell assays were performed to examine cell migration and invasion abilities. Radiotracer-based cellular uptake in vitro and micro-positron emission tomography imaging of liver metastases in vivo were performed. The incidence of liver metastases in LoVo-xenografted mice was significantly higher than that in HT29-xenografted ones. The SUVmax/mean values of F-FMISO, but not F-FDG, in LoVo xenografts were significantly greater than in HT29 xenografts. In vitro, LoVo cells exhibited stronger metastatic potential and higher radiotracer uptake than HT29 cells. Mechanistically, the expression of HIF-1α and GLUT-1 in LoVo cells and LoVo tumor tissues was remarkably higher than in HT29 cells and tissues. Linear regression analysis demonstrated correlations between cellular F-FDG/F-FMISO uptake and HIF-1α/GLUT-1 expression in vitro, as well as between F-FMISO SUVmax and GLUT-1 expression in vivo. F-FMISO uptake may serve as a potential biomarker for the detection of liver metastases in CRC, whereas its clinical use warrants validation.
本研究旨在探讨两种放射性示踪剂(F-氟脱氧葡萄糖(FDG)和 F-氟咪索硝唑(FMISO))在监测人结直肠癌(CRC)肝转移中的应用。通过脾内注射人 CRC 细胞系 LoVo 和 HT29 建立 CRC 肝转移的小鼠模型。进行伤口愈合和 Transwell 分析以检测细胞迁移和侵袭能力。进行放射性示踪剂在体外细胞摄取和体内肝转移微正电子发射断层扫描成像。LoVo 异种移植小鼠的肝转移发生率明显高于 HT29 异种移植小鼠。LoVo 异种移植瘤的 F-FMISO(而非 F-FDG)的 SUVmax/平均值明显大于 HT29 异种移植瘤。体外,LoVo 细胞表现出比 HT29 细胞更强的转移潜能和更高的放射性示踪剂摄取。在机制上,LoVo 细胞和 LoVo 肿瘤组织中 HIF-1α 和 GLUT-1 的表达明显高于 HT29 细胞和组织。线性回归分析表明,体外细胞 F-FDG/F-FMISO 摄取与 HIF-1α/GLUT-1 表达之间,以及体内 F-FMISO SUVmax 与 GLUT-1 表达之间存在相关性。F-FMISO 摄取可能是检测 CRC 肝转移的潜在生物标志物,但其临床应用尚需验证。