title: Vascular permeability during antiangiogenesis treatment: MR imaging assay results as biomarker for subsequent tumor growth in rats.
abstract: OBJECTIVE
  To prospectively evaluate in rats the acute change in tumor vascular leakiness (K(PS)) assayed at magnetic resonance (MR) imaging after a single dose of the angiogenesis inhibitor bevacizumab as a predictive biomarker of tumor growth response after a prolonged treatment course.
  
  
  METHODS
  Institutional animal care and use committee approval was obtained. Seventeen female rats with implanted human breast cancers underwent dynamic albumin-(Gd-DTPA)(30)-enhanced MR imaging followed by an initial dose of bevacizumab or saline (as a control). Treatment was continued every 3rd day, for a total of four doses at five possible dose levels: 0 mg bevacizumab (n = 4 [control rats]), 0.1 mg bevacizumab (n = 3), 0.25 mg bevacizumab (n = 2), 0.5 mg bevacizumab (n = 5), and 1.0 mg bevacizumab (n = 3). A second MR imaging examination was performed 24 hours after the initial dose to enable calculation of the acute change in MR imaging-assayed leakiness, or Delta K(PS). This acute change in K(PS) at MR imaging was correlated with tumor growth response for each cancer at the completion of the 11-day treatment course. For statistical analyses, an unpaired two-tailed t test, analysis of variance, and linear regression analyses were used.
  
  
  RESULTS
  The MR imaging-assayed change in tumor microvascular leakiness, tested as a potential biomarker, correlated strongly with tumor growth rate (R(2) = 0.74, P < .001). K(PS) and tumor growth decreased significantly in all bevacizumab-treated cancers compared with these values in control group cancers (P < .05).
  
  
  CONCLUSIONS
  The MR imaging-assayed acute change in vascular leakiness after a single dose of bevacizumab was an early, measurable predictive biomarker of tumor angiogenesis treatment response.
authors: Department of Radiology, Center for Pharmaceutical and Molecular Imaging, Cardiovascular Research Institute, Comprehensive Cancer Center, University of California San Francisco, CA, USA. hans-juergen.raatschen@charite.de
authors: Hans-Juergen
authors: HJ
authors: Raatschen
authors: Gerhard H
authors: GH
authors: Simon
authors: Yanjun
authors: Y
authors: Fu
authors: Barbara
authors: B
authors: Sennino
authors: David M
authors: DM
authors: Shames
authors: Michael F
authors: MF
authors: Wendland
authors: Donald M
authors: DM
authors: McDonald
authors: Robert C
authors: RC
authors: Brasch
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D007091:Image Processing, Computer-Assisted; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011446:Prospective Studies; D051381:Rats
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003287:Contrast Media; D000068258:Bevacizumab; D019786:Gadolinium DTPA