title: In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Max Planck Institute for Neurological Research, Cologne, Germany. ullrich@nf.mpg.de
authors.forename: Roland T
authors.initials: RT
authors.lastname: Ullrich
authors.forename: Jan F
authors.initials: JF
authors.lastname: Jikeli
authors.forename: Michael
authors.initials: M
authors.lastname: Diedenhofen
authors.forename: Philipp
authors.initials: P
authors.lastname: Böhm-Sturm
authors.forename: Maike
authors.initials: M
authors.lastname: Unruh
authors.forename: Stefan
authors.initials: S
authors.lastname: Vollmar
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000473:pathology*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D010793:Phthalazines; D011725:Pyridines; C404768:vatalanib