title: Contrast-enhanced Ultrasound Imaging of Antiangiogenic Tumor Therapy.
abstract: OBJECTIVE
  Anti-angiogenic treatment is a promising strategy for cancer therapy and is currently evaluated in clinical trials. The aim of the present study was to further investigate the effects of an anti-angiogenic therapy, inhibiting vascular endothelial growth factor (VEGF) and endothelial growth factor (EGF) using a tyrosine kinase inhibitor for blocking tumor angiogenesis and tumor progression in vivo.
  
  
  METHODS
  Experiments were performed using C57/Bl6 mice (25 ± 5 g of body weight (b.w.)) implanted with subcutaneous Lewis lung carcinoma (LLC-1). From day 7 till 21 after tumor cell implantation, animals (n=7 per group) were treated by monotherapy using ZD6474 (50 mg/kg b.w. per os (p.o.)) daily. A control group received only the solvent polysorbate 80. Using contrast enhanced ultrasound (CE-US) parameters of intra-tumoral microcirculation animals were examined 24 h after the last application of ZD6474. Moreover, subcutaneous tumor growth was measured over the whole therapy period. Finally, histological analyses were performed to analyze the functional vessel density in the tumor tissue.
  
  
  RESULTS
  ZD6474 reduced tumor growth of LLC-1 in C57/Bl6 mice significantly. A significant difference of maximal signal intensity (ΔSImax) and area below the intensity time curve (AUC) after antiangiogenic therapy was recorded in the tumor center by CE-US. Vessel density after hematoxyline and eosin, as well as CD31, staining showed no significant difference in both groups.
  
  
  CONCLUSIONS
  Anti-angiogenic effects can be quantitatively demonstrated using CE-US imaging, which represents the spreading of efficient vessels in the tumor tissue, especially in the tumor center.
authors.affiliation: Clinic of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany Walter-Brendel-Centre of Experimental Medicine, University of Munich, Munich, Germany Laura.Klotz@med.uni-muenchen.de.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Klotz
authors.affiliation: Department of Clinical Radiology, University of Munich, Munich, Germany.
authors.forename: Dirk-Andre
authors.initials: DA
authors.lastname: Clevert
authors.affiliation: Walter-Brendel-Centre of Experimental Medicine, University of Munich, Munich, Germany.
authors.forename: Siiri
authors.initials: S
authors.lastname: Scheckinger
authors.affiliation: Department of Otorhinolaryngology, University of Mainz, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Strieth
authors.affiliation: Walter-Brendel-Centre of Experimental Medicine, University of Munich, Munich, Germany Department of Thoracic Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Eichhorn
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D003287:Contrast Media / Q000008:administration & dosage; D003952:Diagnostic Imaging; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D016228:Endothelial Growth Factors; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A
keywords: Anti-angiogenic therapy; ZD6474; angiogenesis; contrast enhanced ultrasound; imaging; tumor microcirculation; vessel density