18F-FMISO PET显像评价结直肠癌肝转移的实验研究

目的探究^18F-FMISO PET定量参数(肿瘤/肝脏SUVmax)在检测小鼠CRC肝转移潜能中的应用价值。方法采用伤口愈合实验检测CRC细胞迁移能力,采用细胞摄取实验检测体外^18F-FMISO摄取能力。建立肝转移及皮下移植瘤小鼠模型以进行Micro-PET显像和定量分析。采用皮尔森相关系数分析18F-FMISO参数、肝转移数量及生物学指标(HIF-1α、GLUT-1)之间的相关性。结果在HT29、HCT116及LoVo三种肝转移模型中,LoVo小鼠具有更高的肝转移率及较短的中位生存时间。与HT29和HCT116细胞相比,LoVo细胞具有更强的迁移能力和更高的18F-FMISO体外摄取能力。体内Micro-PET显像表明,LoVo肝转移模型及皮下荷瘤模型的T/L SUVmax值明显高于HT29和HCT116模型。相关性分析显示,肝转移瘤的18F-FMISO T/L SUVmax值与肝转移瘤(直径大于0.5 cm)数量存在显著相关性(r=0.6408,P=0.0013),与HIF-1α(r=0.8145,P=0.0075)和GLUT-1(r=0.8252,P=0.0062)表达也存在显着相关性。结论18F-FMISO定量参数T/L SUVmax在动物模型中为评价CRC肝转移提供了有价值的分子影像信息,其在预测CRC肝转移潜能方面具有一定的应用价值。

18F-FMISO PET evaluation of liver metastasis from colorectal cancer in mice

Objective To assess the value of ^18F-fluoromisonidazole (FMISO) positron emission tomography (PET) for detecting liver metastasis from human colorectal cancer in mice. Methods Wound healing assays were performed to examine the ability of cell migration in vitro. ^18F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^18F-FMISO micro-PET imaging of liver metastasis in mice with human colorectal cancer was performed. The tumor-to-liver ratio of maximum standard uptake values (SUVmax) was calculated. The correlation between the ^18F-FMISO SUVmax ratio, number of liver metastases, hypoxia-induced HIF-1α, and serum starvation-induced GLUT-1 was evaluated using Pearson correlation analysis. Results Compared with HT29 and HCT116, LoVo-CLM mice had significantly higher liver metastasis 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, ^18F-FMISO SUVmax ratio was significantly higher in both LoVo-CLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. Linear regression analysis showed significant correlation between ^18F-FMISO SUVmax ratio of CLM-mice and number of liver metastases larger than 0.5 cm (r=0.6408, P=0.0013), as well as between ^18F-FMISO SUVmax ratio and HIF-1α (r=0.8145, P=0.0075) or GLUT-1 (r=0.8252, P=0.0062) expression in tumor-bearing tissues. Conclusion 18F-FMISO PET imaging parameter of SUVmax ratio provides tumor biological information and may be a marker for predicting liver metastasis from colorectal cancer.