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

Vascular permeability during antiangiogenesis treatment: MR imaging assay results as biomarker for subsequent tumor growth in rats.

Author information

1
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

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.

PMID:
18372448
PMCID:
PMC4423757
DOI:
10.1148/radiol.2472070363
[Indexed for MEDLINE]
Free PMC Article

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