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

Mingyu Zhang,Hailong Xu,Yiqiao Wang,Hao Jiang,Wenbin Pan,Song Wang,Huijie Jiang,Rongjun Zhang,Xin Li

doi:10.1038/s41598-018-36238-x

Abstract

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.

Highlights

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, accounting for 10% of all malignancies[1,2]
This study aimed to investigate whether 18F-FDG- and 18F-FMISO-based Positron emission tomography (PET) can be used to monitor the colorectal liver metastases (CLM) derived from the colorectal cancer (CRC) cell lines LoVo and HT29, which have different metastatic potentials, by assessing the correlation between radiotracer uptake and tumor marker expression in vitro and in vivo
We investigated the use of 18F-FDG/18F-FMISO-based PET imaging in CLM mouse models and demonstrated that LoVo cells have a stronger metastatic potential than HT29 cells

Summary

Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, accounting for 10% of all malignancies[1,2]. 18F-FDG/18F-FMISO-based PET imaging is used in tumor staging and follow-up examination of multiple malignancies including glioblastoma[15], head and neck cancer[16], lung cancer[17], breast cancer[18], and CRC19. These radiotracers have not been applied to monitor CLM yet. This study aimed to investigate whether 18F-FDG- and 18F-FMISO-based PET can be used to monitor the CLM derived from the CRC cell lines LoVo and HT29, which have different metastatic potentials, by assessing the correlation between radiotracer uptake and tumor marker expression in vitro and in vivo

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Conclusion