Vascular Permeability During Antiangiogenesis Treatment: MR Imaging Assay Results as Biomarker for Subsequent Tumor Growth in Rats

Radiology. 2008 May;247(2):391-9. doi: 10.1148/radiol.2472070363. Epub 2008 Mar 27.

Abstract

Purpose: 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.

Materials and 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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Analysis of Variance
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Biomarkers, Tumor / analysis
  • Contrast Media
  • Female
  • Gadolinium DTPA
  • Image Processing, Computer-Assisted
  • Least-Squares Analysis
  • Magnetic Resonance Imaging*
  • Mammary Neoplasms, Experimental / blood supply*
  • Mammary Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Prospective Studies
  • Rats

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Contrast Media
  • Bevacizumab
  • Gadolinium DTPA