Micro-positron emission tomography imaging of angiogenesis based on 18F-RGD for assessing liver metastasis of colorectal cancer

Hepatobiliary Pancreat Dis Int. 2021 Aug;20(4):345-351. doi: 10.1016/j.hbpd.2021.03.001. Epub 2021 Mar 9.

Abstract

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 18F-AIF-NOTA-E[PEG4-c(RGDfk)]2 (denoted as 18F-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 18F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio. Pearson correlation 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 18F-RGD showed a moderate correlation 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 18F-RGD SUVmean ratio, SUVmax ratio for differentiating LoVo from LS174T tumor were 0.801 and 0.759, respectively.

Conclusions: The tumor-to-liver SUVmean ratio of 18F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.

Keywords: Colorectal liver metastases; Positron emission tomography; RGD peptide; Vascular endothelial growth factor.

MeSH terms

  • Animals
  • Colorectal Neoplasms* / diagnostic imaging
  • Fluorodeoxyglucose F18
  • Ki-67 Antigen
  • Liver Neoplasms* / diagnostic imaging
  • Mice
  • Neovascularization, Pathologic / diagnostic imaging
  • Oligopeptides
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Tumor Microenvironment
  • Vascular Endothelial Growth Factor A

Substances

  • Ki-67 Antigen
  • Oligopeptides
  • Radiopharmaceuticals
  • Vascular Endothelial Growth Factor A
  • Fluorodeoxyglucose F18