title: Non-invasive quantification of anti-angiogenic therapy by contrast-enhanced MRI in experimental pancreatic cancer.
abstract: BACKGROUND
  Currently, early changes of tumor vasculature after angiogenesis inhibition can only be evaluated by histopathology, a method not suitable in a clinical setting.
  
  
  OBJECTIVE
  To quantify effects of different angiogenesis inhibitors on the microvasculature of orthotopically implanted pancreatic cancers by contrast-enhanced magnetic resonance imaging (MRI) in order to establish a non-invasive technique for monitoring antiangiogenic cancer treatment.
  
  
  METHODS
  DSL-6A/C1 pancreatic cancers were implanted in the pancreas of 109 Lewis rats. Three weeks later, antiangiogenic treatment was initiated by administration of Bevacizumab (n = 38) or Suramin (n = 27) while the control group (n = 44) remained untreated. Dynamic MRI was performed 24 h, 1 week, and 4 weeks after treatment initiation. Fractional tumor plasma volume (fPV, %) and vascular permeability (K(PS), mL/min/100 cc) were calculated based on the MRI data by using a pharmacokinetic model.
  
  
  RESULTS
  Twenty-four hours after the initial dose, a significant decline in K(PS) was observed in the Bevacizumab group compared to the control and Suramin group (0.002 ± 0.008; 0.057 ± 0.046 and 0.064 ± 0.062 (mean ± SD); P < 0.05). At 1 week, fPV was significantly smaller in Bevacizumab and Suramin treated tumors compared to control tumors (6.25 ± 2.74, 7.47 ± 3.44, and 15.10 ± 9.97, respectively; P < 0.05). Differences in tumor volumes were first observed after 4 weeks of treatment with significantly larger control tumors (4380.3 ± 1590.6 vs. 869.6 ± 717.2 and 1676.5 ± 2524.1 mm(3); P < 0.05).
  
  
  CONCLUSIONS
  Dynamic MRI can quantify antiangiogenic effects on tumor microvasculature before changes in tumor volumes are detectable. Thus, this technique is a reasonable addition to morphological MRI and may be applied as an alternative to histopathology.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Raatschen
authors.forename: Susanne
authors.initials: S
authors.lastname: Fischer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Zsivcsec
authors.forename: Christian-Olaf
authors.initials: CO
authors.lastname: Schoenfeld
authors.forename: Birgit
authors.initials: B
authors.lastname: Hotz
authors.forename: Heinz J
authors.initials: HJ
authors.lastname: Buhr
authors.forename: Hubert G
authors.initials: HG
authors.lastname: Hotz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D008297:Male; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013498:Suramin / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003287:Contrast Media; D000068258:Bevacizumab; D013498:Suramin; D019786:Gadolinium DTPA
keywords: Experimental investigations; MR functional imaging; animal investigations; pancreas; treatment effects