title: Combination therapy of radiofrequency ablation and bevacizumab monitored with power Doppler ultrasound in a murine model of hepatocellular carcinoma.
abstract: OBJECTIVE
  The purpose of this study was to monitor tumour blood flow with power Doppler ultrasound following antiangiogenic therapy with bevacizumab in order to optimally time the application of radiofrequency (RF) ablation to increase ablation diameter.
  
  
  METHODS
  Athymic nude mice bearing human hepatocellular carcinoma xenografts were treated with bevacizumab and imaged daily with power Doppler ultrasound to quantify tumour blood flow. Mice were treated with RF ablation alone or in combination with bevacizumab at the optimal time, as determined by ultrasound. Ablation diameter was measured with histology and tumour microvascular density was calculated with immunohistochemistry. A computational thermal model of RF ablation was used to estimate ablation volume.
  
  
  RESULTS
  A maximum reduction of 27.8 ± 8.6% in tumour blood flow occurred on day 2 following antiangiogenic therapy, while control tumours increased 29.3 ± 17.1% (p < 0.05). Tumour microvascular density was similarly reduced by 45.1 ± 5.9% on day 2 following antiangiogenic therapy. Histology demonstrated a 13.6 ± 5.6% increase in ablation diameter (40 ± 21% increase in volume) consistent with a computational model.
  
  
  CONCLUSIONS
  Quantitative power Doppler ultrasound is a useful biomarker to monitor tumour blood flow following antiangiogenic treatment and to guide the application of RF ablation as a drug plus device combination therapy.
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ashesh A
authors.initials: AA
authors.lastname: Thaker
authors.forename: Faezeh
authors.initials: F
authors.lastname: Razjouyan
authors.forename: David L
authors.initials: DL
authors.lastname: Woods
authors.forename: Dieter
authors.initials: D
authors.lastname: Haemmerich
authors.forename: Kiran
authors.initials: K
authors.lastname: Sekhar
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging / Q000628:therapy*; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D012039:Regional Blood Flow; D018608:Ultrasonography, Doppler; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab