Background: Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment. This study aimed to explore the feasibility of F-18-AIF-NOTA-E[PEG(4)-c(RGDfk)](2) (denoted as F-18-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential. Methods: Twenty LoVo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection. Radiotracer-based micro-PET imaging of animal model was performed and the uptake of F-18-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio. Pearson cor-relation was used to analyze the relationship between radioactive parameters and tumor markers. Results: The SUVmax and SUVmean ratios of LoVo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions ( P < 0.05). A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between LoVo and LS174T primary tumors ( P < 0.05). The tumor-to-liver SUVmax or SUVmean ratio of F-18-RGD showed a moderate cor-relation with VEGF expression ( r = 0.5700, P = 0.001 and r = 0.6657, P < 0.001, respectively), but the SUVmean ration showed a weak correlation with Ki67 expression ( r = 0.3706, P < 0.05). The areas under the receiver operating characteristic (ROC) curves of F-18-RGD SUVmean ratio, SUVmax ratio for differen-tiating LoVo from LS174T tumor were 0.801 and 0.759, respectively. Conclusions: The tumor-to-liver SUVmean ratio of F-18-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model. (C) 2021 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.