Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Key Laboratory of Nuclear Medicine of the Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Hepatobiliary Pancreat Dis Int. 2019 Apr;18(2):164-172. doi: 10.1016/j.hbpd.2019.02.008. Epub 2019 Feb 26.
Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of F-fluoromisonidazole (FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer (CRC) in mice.
Colorectal liver metastases (CRLM) xenograft models were established by injecting tumor cells (LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1α) and serum starvation-induced glucose transporter 1 (GLUT-1) was evaluated using Pearson correlation analysis.
Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues.
F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
正电子发射断层扫描（PET）成像是一种非侵入性的功能成像方法，用于反映肿瘤的空间信息，并提供肿瘤进展的生物学特征。本研究旨在关注 F-氟代米索硝唑（FMISO）PET 最大标准化摄取值（SUVmax）比值的定量参数在检测人结直肠癌（CRC）在小鼠中肝转移潜能的应用。
通过将肿瘤细胞（LoVo、HT29 和 HCT116）注入小鼠脾脏中建立结直肠肝转移（CRLM）异种移植模型，通过将肿瘤细胞皮下注射到小鼠右左腰部建立荷瘤异种移植模型。通过划痕实验检测细胞迁移能力。通过细胞摄取实验测量 CRC 细胞系中 F-FMISO 的摄取。对 CRLM 和荷瘤小鼠进行 F-FMISO 基于微 PET 的成像，并通过肿瘤与肝脏 SUVmax 比值进行定量。使用 Pearson 相关分析评估 F-FMISO SUVmax 比值与肝转移数量、缺氧诱导因子 1α（HIF-1α）和血清饥饿诱导葡萄糖转运蛋白 1（GLUT-1）之间的相关性。
与 HT29 和 HCT116 相比，LoVo-CRLM 小鼠的肝转移比例明显更高，中位生存时间更短。LoVo 细胞在体外的迁移能力和放射性示踪剂摄取均强于 HT29 和 HCT116。此外，与 HT29 和 HCT116 建立的模型相比，LoVo-CRLM 模型和 LoVo 荷瘤模型的 F-FMISO SUVmax 比值均显著升高。此外，Pearson 相关分析显示，CRLM 小鼠的 F-FMISO SUVmax 比值与大于 0.5cm 的肝转移数量之间存在显著相关性，以及与肿瘤组织中 HIF-1α或 GLUT-1 表达之间存在显著相关性。
F-FMISO SUVmax 比值参数可为 CRLM 小鼠提供有用的肿瘤生物学信息，从而更好地预测 CRLM，并为预测 CRC 的肝转移潜能提供有用的放射性标记物。
