title: Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging.
abstract: OBJECTIVE
  To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response.
  
  
  METHODS
  In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging. DCE-MRI data were analyzed applying a two-compartment model (Brix), calculating the parameters Amplitude and k(ep).
  
  
  RESULTS
  For both experiments Amplitude decreased significantly in treated tumors while k(ep) did not change significantly. VSI showed controversial results. VSI was significantly increased in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab-treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and suggest differences in the maturation of tumor vascularization as a possible explanation.
  
  
  CONCLUSIONS
  DCE-MRI and vessel size imaging provide reliable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in excellent agreement with histology. Nevertheless, our results also indicate that vascular remodeling is complex and that a uniform response cannot be expected for different tumors and therapies.
authors.affiliation: Siemens AG, Healthcare Sector, Erlangen, Germany. s.zwick@dkfz.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zwick
authors.forename: Ralph
authors.initials: R
authors.lastname: Strecker
authors.forename: Valerji
authors.initials: V
authors.lastname: Kiselev
authors.forename: Peter
authors.initials: P
authors.lastname: Gall
authors.forename: Jochen
authors.initials: J
authors.lastname: Huppert
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.forename: Eva C
authors.initials: EC
authors.lastname: Woenne
authors.forename: Arne
authors.initials: A
authors.lastname: Hengerer
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D003287:Contrast Media; D005260:Female; D007211:Indoles / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology*; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib