Noninvasive evaluation of 18F-FDG/18F-FMISO-based Micro PET in monitoring hepatic metastasis of colorectal cancer

Noninvasive evaluation of 18F-FDG/18F-FMISO-based Micro PET in monitoring hepatic metastasis of colorectal cancer
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基于(18)F-FDG/(18)F-FMISO的Micro PET监测结直肠癌肝转移的无创评估。

DOI:
10.1038/s41598-018-36238-x
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发表时间:
2018-12
期刊:
影响因子:
4.6
通讯作者:
Song Wang
Song Wang
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mingyu Zhang;Huijie Jiang;Rongjun Zhang;Hailong Xu;Hao Jiang;Wenbin Pan;Xin Li;Yiqiao Wang;Song Wang

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本研究旨在探讨两种放射性示踪剂(18F-氟脱氧葡萄糖(FDG)和18F-氟米索硝唑(FMISO))在监测人结直肠癌(CRC)肝转移中的应用。通过脾内注射植入人结直肠癌细胞系 LoVo 和 HT29 建立结直肠癌肝转移小鼠模型。进行伤口愈合和Transwell实验来检查细胞迁移和侵袭能力。进行了基于放射性示踪剂的体外细胞摄取和体内肝转移的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显着高于HT29异种移植小鼠。 LoVo 异种移植物中 18F-FMISO(而非 18F-FDG)的 SUVmax/平均值显着大于 HT29 异种移植物。在体外,LoVo 细胞比 HT29 细胞表现出更强的转移潜力和更高的放射性示踪剂摄取。从机制上看,LoVo细胞和LoVo肿瘤组织中HIF-1α和GLUT-1的表达显着高于HT29细胞和组织。线性回归分析证明了体外细胞 18F-FDG/18F-FMISO 摄取与 HIF-1α/GLUT-1 表达之间以及体内 18F-FMISO SUVmax 与 GLUT-1 表达之间的相关性。 18F-FMISO 摄取可作为检测 CRC 肝转移的潜在生物标志物,而其临床应用值得验证。
This study aimed to explore the application of two radiotracers (18F-fluorodeoxyglucose (FDG) and 18F-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 18F-FMISO, but not 18F-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 18F-FDG/18F-FMISO uptake and HIF-1α/GLUT-1 expression in vitro, as well as between 18F-FMISO SUVmax and GLUT-1 expression in vivo. 18F-FMISO uptake may serve as a potential biomarker for the detection of liver metastases in CRC, whereas its clinical use warrants validation.
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