title: Effect of an angiogenesis inhibitor on hepatic tumor perfusion and the implications for adjuvant cytotoxic therapy.
abstract: OBJECTIVE
  To determine whether dynamic contrast material-enhanced (DCE) computed tomography (CT) can help identify hepatic tumor perfusion response to vascular remodeling induced by antiangiogenesis treatment in a rabbit model.
  
  
  METHODS
  The study was approved by the Animal Use Subcommittee of the University Council on Animal Care. DCE CT hepatic perfusion measurements were performed in the livers of 20 rabbits implanted with VX2 carcinoma. Vascular remodeling was induced with thalidomide dissolved in dimethyl sulfoxide and sterile water, starting at a tumor diameter of 0.7 cm±0.1 and continuing until metastatic lung nodules were observed. The control group (n=8) was given an equivalent volume of the vehicle. The therapy group was subdivided into animals that survived for more than 24 days without lung metastasis (responder group, n=5) or those that survived for less than 24 days (nonresponder group, n=7). Data were analyzed with the Kruskal-Wallis or Friedman rank test and reported as medians and interquartile ranges.
  
  
  RESULTS
  DCE CT depicted differential perfusion change within the therapy group after treatment. By day 4, hepatic blood volume (HBV) in the responder group decreased by 29.2% (-32.5% to -11.8%) relative to that before treatment and was significantly different from that in the nonresponder (P=.048) and control (P=.011) groups, where HBV remained stable. By day 8, hepatic artery blood flow decreased by 50.0% (-59.08% to -21.05%) relative to that before treatment in the responder group and was significantly different from that in the nonresponder and control groups (P=.030 for both), which remained stable at -3.5% (-8.5% to 28.7%, P=.50) and -10.0% (-33.8% to 10.4%, P=.48), respectively.
  
  
  CONCLUSIONS
  DCE CT can help differentiate responders from nonresponders by their early differential perfusion response to antiangiogenesis therapy.
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Errol E
authors.initials: EE
authors.lastname: Stewart
authors.forename: Hongtao
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schafer
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Bertha M
authors.initials: BM
authors.lastname: Garcia
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007472:Iohexol; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D008297:Male; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011817:Rabbits; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013792:Thalidomide; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D007472:Iohexol; D013792:Thalidomide