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Characterization of bevacizumab dose response relationship in U87 brain tumors using magnetic resonance imaging measures of enhancing tumor volume and relative cerebral blood volume

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

Despite the early promising results with the anti-angiogenic agent, bevacizumab, to prolong time to progression in patients with brain tumors, the optimal dose and drug combinations have not yet been defined. The purpose of this study was to characterize the bevacizumab dose–response relationship for brain tumors by measuring the contrast-agent enhanced tumor volumes and relative cerebral blood volume (rCBV) using dynamic susceptibility contrast (DSC) imaging. The studies, performed in the U87 brain tumor model using doses of bevacizumab ranging from 0 to 10 mg/kg, demonstrate that tumor growth and vascularity are inhibited at all doses used, compared to untreated controls. However, only the maximum dose showed a statistically significant difference in growth rate. Conversely tumor vascularity, as measured with rCBV, was inhibited equally well for all doses used with no clear indication that higher doses are more effective.

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Acknowledgments

The authors thank Genentech for the generous gift of Avastin and R. Harris and M. Runquist for technical assistance. This work was supported by National Institute of Health Grant CA-082500 to K.M. Schmainda and MCW Advancing Healthier Wisconsin/Translational Brain Tumor Research Program.

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Authors and Affiliations

  1. Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, WI, USA

    Kimberly R. Pechman, Deborah L. Donohoe, Devyani P. Bedekar, Shekar N. Kurpad & Kathleen M. Schmainda

  2. Department of Neurosurgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Kimberly R. Pechman & Shekar N. Kurpad

  3. Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Deborah L. Donohoe, Devyani P. Bedekar & Kathleen M. Schmainda

  4. Clement J Zablocki VA Medical Center, Milwaukee, WI, USA

    Shekar N. Kurpad

  5. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Raymond G. Hoffmann

  6. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA

    Kathleen M. Schmainda

Authors
  1. Kimberly R. Pechman
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  2. Deborah L. Donohoe
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  3. Devyani P. Bedekar
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  4. Shekar N. Kurpad
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  6. Kathleen M. Schmainda
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Correspondence to Kimberly R. Pechman.

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Pechman, K.R., Donohoe, D.L., Bedekar, D.P. et al. Characterization of bevacizumab dose response relationship in U87 brain tumors using magnetic resonance imaging measures of enhancing tumor volume and relative cerebral blood volume. J Neurooncol 105, 233–239 (2011). https://doi.org/10.1007/s11060-011-0591-8

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  • DOI: https://doi.org/10.1007/s11060-011-0591-8

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