Molecular Imaging of Tumor Angiogenesis and Therapeutic Effects with Dual Bioluminescence

Curr Pharm Biotechnol. 2017;18(5):422-428. doi: 10.2174/1389201018666170523165053.

Abstract

Background: Angiogenesis is critical for the growth of tumor by supplying nutrients and oxygen that exacerbates the metastasis and progression of cancer. Noninvasive imaging of angiogenesis during the tumor therapeutic processes may provide novel opportunities for image-guided tumor management.

Objective: Here, we want to develop a mouse animal model for assessing cancer progression and angiogenesis in the same individuals by molecular imaging.

Methods: Breast cancer model was developed with mouse breast cancer cell line 4T1 carrying a reporter system encoding a triple fusion (TF) reporter gene consisting of renilla luciferase (Rluc), red fluorescent protein (RFP) and herpes simplex virus truncated thymidine kinase (HSV-ttk) in transgenic mice, which expressed firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc). The mice were subsequently treated with ganciclovir (GCV) and the tumor angiogenesis was tracked by Fluc imaging and the growth status of tumor was monitored by imaging of Rluc simultaneously.

Conclusion: Overall, this traceable breast cancer model can simultaneously image the tumor growth and angiogenesis in single individual, which may facilitate a better understanding the mechanisms of angiogenesis in the progression and regression of tumor.

Keywords: Angiogenesis; VEGF receptor (VEGFR); bioluminescence imaging (BLI); firefly luciferase (Fluc); renilla luciferase (Rluc); vascular endothelial growth factor (VEGF).

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Genes, Reporter
  • Humans
  • Luciferases, Renilla / genetics
  • Luminescent Measurements / methods*
  • Luminescent Proteins / genetics
  • Male
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / diagnostic imaging*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Transgenic
  • Molecular Imaging / methods*
  • Neovascularization, Pathologic / diagnostic imaging*
  • Neovascularization, Pathologic / metabolism
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Simplexvirus / enzymology
  • Thymidine Kinase / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Luminescent Proteins
  • Vascular Endothelial Growth Factor A
  • red fluorescent protein
  • Luciferases, Renilla
  • Thymidine Kinase
  • Receptors, Vascular Endothelial Growth Factor