title: Monitoring of bevacizumab-induced antiangiogenic treatment effects by "steady state" ultrasmall superparamagnetic iron oxide particles magnetic resonance imaging using robust multiecho ΔR2* relaxometry.
abstract: OBJECTIVE
  The purpose of this study was to evaluate whether "steady state" magnetic resonance imaging (MRI) using a robust multiecho ΔR2* MR relaxometry technique is suitable for the early assessment of a clinically approved antiangiogenic treatment regimen using bevacizumab (Avastin).
  
  
  METHODS
  A673 rhabdomyosarcoma-bearing mice were treated with bevacizumab (n = 6) or saline as control, respectively (n = 6). MRI using a multigradient echo sequence was performed before and after 2 doses of 100 μg bevacizumab at baseline and day 7. Ultrasmall superparamagnetic iron oxide particles (SH U 555 C) induced changes of the transverse relaxation rate R2* (ΔR2*) were measured in regions of interest. From these results, the vascular volume fraction was estimated, providing a surrogate marker for the microvessel density (MVD). The actual MVD was determined by immunohistochemistry and correlated with the MRI results.
  
  
  RESULTS
  Bevacizumab treatment resulted in a significant reduction of the ΔR2* values compared with the control group (bevacizumab: 10.47 ± 0.78 seconds(-1) vs. control: 17.91 ± 2.63 seconds(-1); P = 0.01), reflecting the significant decrease of the vascular volume fraction by 33% (bevacizumab: 2.21% ± 0.15% vs. control: 3.31% ± 0.22%; P = 0.001). Immunohistochemistry confirmed the MR results showing an approximately 25% reduction of the MVD after treatment (bevacizumab: 7.11 ± 0.3 vs. control: 9.45 ± 0.38; P = 0.001).
  
  
  CONCLUSIONS
  Multiecho ΔR2* MR relaxometry allows an early and quantitative assessment of tumor vascularization changes in response to an antiangiogenic treatment with a clinically approved vascular endothelial growth factor inhibitor. With the availability of long circulating ultrasmall superparamagnetic iron oxide particles s for clinical use, this imaging technique could be instantly translated to antiangiogenic treatment monitoring in clinical studies.
authors.affiliation: Department of Clinical Radiology, University of Muenster, Germany. Janine.Ring@gmx.de
authors.forename: Janine
authors.initials: J
authors.lastname: Ring
authors.forename: Thorsten
authors.initials: T
authors.lastname: Persigehl
authors.forename: Stefanie
authors.initials: S
authors.lastname: Remmele
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.forename: Hannes
authors.initials: H
authors.lastname: Dahnke
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003287:Contrast Media; D005260:Female; D005290:Ferric Compounds; D052203:Ferrosoferric Oxide; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy*; D013223:Statistics as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D005290:Ferric Compounds; D000068258:Bevacizumab; D052203:Ferrosoferric Oxide