title: Use of VEGFR-2 targeted ultrasound contrast agent for the early evaluation of response to sorafenib in a mouse model of hepatocellular carcinoma.
abstract: OBJECTIVE
  The aim of this study was to assess the early response to sorafenib using ultrasound molecular imaging in a murine model of hepatocellular carcinoma (HCC).
  
  
  METHODS
  A xenograft model of HCC was established. Then, mice were divided in two groups and received treatment (sorafenib) or placebo for 14 days. The treatment group was further divided into non-responders and responders according to the degree of growth. Contrast enhanced ultrasound (CEUS) was performed using VEGFR-2 targeted microbubbles (BR55, Bracco Suisse SA, Geneva, Switzerland). Dedicated software was used to quantify the amount of bound microbubbles in the tumor as a numerical value (differential targeted enhancement (dTE)). Tumors were then excised and western blot analysis performed.
  
  
  RESULTS
  The dTE values decreased from day 0 to day +14 both in the treatment and control groups, but were lower in the former. The non-responder group had higher dTE levels at day 2 compared to responders (p = 0.019).
  
  
  CONCLUSIONS
  BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.
authors.affiliation: Department of Veterinary Medical Sciences, Alma Mater Studiorum, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Baron Toaldo
authors.forename: Veronica
authors.initials: V
authors.lastname: Salvatore
authors.forename: Sara
authors.initials: S
authors.lastname: Marinelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Palamà
authors.forename: Maddalena
authors.initials: M
authors.lastname: Milazzo
authors.forename: Luca
authors.initials: L
authors.lastname: Croci
authors.forename: Laura
authors.initials: L
authors.lastname: Venerandi
authors.forename: Mario
authors.initials: M
authors.lastname: Cipone
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Fabio
authors.initials: F
authors.lastname: Piscaglia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D051379:Mice; D045423:Microbubbles; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011897:Random Allocation; D012984:Software; D000077157:Sorafenib; D016896:Treatment Outcome; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
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