title: Monitoring antivascular therapy in head and neck cancer xenografts using contrast-enhanced MR and US imaging.
abstract: BACKGROUND
  The overall goal of this study was to non-invasively monitor changes in blood flow of squamous cell carcinoma of the head and neck (SCCHN) xenografts using contrast-enhanced magnetic resonance (MR) and ultrasound (US) imaging.
  
  
  METHODS
  Experimental studies were performed on mice bearing FaDu tumors and SCCHN xenografts derived from human surgical tissue. MR examinations were performed using gadofosveset trisodium at 4.7T. Change in T1-relaxation rate of tumors (ΔR1) and tumor enhancement parameters (amplitude, area under the curve-AUC) were measured at baseline and 24 h after treatment with a tumor-vascular disrupting agent (tumor-VDA), 5,6-dimethylxanthenone-4-acetic acid (DMXAA; ASA404) and correlated with tumor necrosis and treatment outcome. CE-US was performed using microbubbles (Vevo MicroMarker®) to assess the change in relative tumor blood volume following VDA treatment.
  
  
  RESULTS
  A marked decrease (up to 68% of baseline) in T1-enhancement of FaDu tumors was observed 1 day after VDA therapy indicative of a reduction in blood flow. Early (24 h) vascular response of individual tumors to VDA therapy detected by MRI correlated with tumor necrosis and volume estimates at 10 days post treatment. VDA treatment also resulted in a significant reduction in AUC and amplitude of patient tumor-derived SCCHN xenografts. Consistent with MRI observations, CE-US revealed a significant reduction in tumor blood volume of patient tumor-derived SCCHN xenografts after VDA therapy. Treatment with VDA resulted in a significant tumor growth inhibition of patient tumor derived SCCHN xenografts.
  
  
  CONCLUSIONS
  These findings demonstrate that both CE-MRI and CE-US allow monitoring of early changes in vascular function following VDA therapy. The results also demonstrate, for the first time, potent vascular disruptive and antitumor activity of DMXAA against patient tumor-derived head and neck carcinoma xenografts.
authors: Department of Pharmacology and Therapeutics, Preclinical Imaging Laboratory, Roswell Park Cancer Institute, Buffalo, NY, USA. Mukund.Seshadri@roswellpark.org
authors: Mukund
authors: M
authors: Seshadri
authors: Nuno T
authors: NT
authors: Sacadura
authors: Tonya
authors: T
authors: Coulthard
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000000981:diagnostic imaging; D005260:Female; D005682:Gadolinium; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging; D006801:Humans; D018810:Magnetic Resonance Angiography; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009942:Organometallic Compounds; D014183:Transplantation, Heterologous; D014463:Ultrasonography; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; D044004:Xanthones; C066668:vadimezan; D005682:Gadolinium; C109932:gadofosveset trisodium