In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice

PLoS One. 2011 May 5;6(5):e19592. doi: 10.1371/journal.pone.0019592.

Abstract

Purpose: Inhibition of angiogenesis has shown clinical success in patients with cancer. Thus, imaging approaches that allow for the identification of angiogenic tumors and the detection of response to anti-angiogenic treatment are of high clinical relevance.

Experimental design: We established an in vivo magnetic resonance imaging (MRI) approach that allows us to simultaneously image tumor microvessel density and tumor vessel size in a NSCLC model in mice.

Results: Using microvessel density imaging we demonstrated an increase in microvessel density within 8 days after tumor implantation, while tumor vessel size decreased indicating a switch from macro- to microvessels during tumor growth. Moreover, we could monitor in vivo inhibition of angiogenesis induced by the angiogenesis inhibitor PTK787, resulting in a decrease of microvessel density and a slight increase in tumor vessel size.

Conclusions: We present an in vivo imaging approach that allows us to monitor both tumor microvessel density and tumor vessel size in the tumor. Moreover, this approach enables us to assess, early-on, treatment effects on tumor microvessel density as well as on tumor vessel size. Thus, this imaging-based strategy of validating anti-angiogenic treatment effects has high potential in applications to preclinical and clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Humans
  • Magnetic Resonance Imaging*
  • Mice
  • Microvessels / drug effects
  • Microvessels / pathology*
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Phthalazines
  • Pyridines
  • vatalanib