18F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis

Abstract

Background: 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 ¹⁸F-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.

Methods: 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. ¹⁸F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ¹⁸F-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 ¹⁸F-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.

Results: 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, ¹⁸F-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 ¹⁸F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ¹⁸F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues.

Conclusions: ¹⁸F-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.

Keywords: (18)F-FMISO; Colorectal liver metastases; Heterogeneity; Positron emission tomography.