Original Research

MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model

  1. S.O. Aliu BS1,2,*,
  2. L.J. Wilmes PhD1,
  3. M.M. Moasser MD3,
  4. B.C. Hann MD, PhD4,
  5. K.-L. Li PhD1,
  6. D. Wang BS4,
  7. N.M. Hylton PhD1,2

Article first published online: 22 APR 2009

DOI: 10.1002/jmri.21737

Issue

Journal of Magnetic Resonance Imaging

Journal of Magnetic Resonance Imaging

Volume 29, Issue 5, pages 1071–1079, May 2009

Additional Information

How to Cite

Aliu, S.O., Wilmes, L.J., Moasser, M.M., Hann, B.C., Li, K.-L., Wang, D. and Hylton, N.M. (2009), MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model. J. Magn. Reson. Imaging, 29: 1071–1079. doi: 10.1002/jmri.21737

Author Information

  1. 1

    Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, California

  2. 2

    Joint Graduate Group in Bioengineering, University of California at Berkeley and San Francisco, California

  3. 3

    Department of Medicine, University of California at San Francisco, San Francisco, California

  4. 4

    Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California

*UCSF Department of Radiology, Box 0946, San Francisco CA, 94107

Publication History

  1. Issue published online: 22 APR 2009
  2. Article first published online: 22 APR 2009
  3. Manuscript Accepted: 9 JAN 2009
  4. Manuscript Received: 3 SEP 2008

Funded by

  • National Institutes of Health (NIH). Grant Number: R01 CA059487

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Keywords:

  • chemotherapy;
  • dynamic contrast enhanced;
  • diffusion weighted imaging;
  • gefitinib;
  • tyrosine kinase inhibitor;
  • xenograft tumor model

Abstract

Purpose

To evaluate whether quantitative MRI parameters are sensitive to the effects of the tyrosine kinase inhibitor gefitinib and can discriminate between two different treatment protocols.

Materials and Methods

Untreated mice with BT474 breast tumor xenografts were characterized in a preliminary study. Subsequently, tumor volume, apparent diffusion coefficient (ADC), transendothelial permeability (Kps), and fractional plasma volume (fPV) were measured in three groups of mice receiving: 1) control vehicle for 10 days, or gefitinib as 2) a single daily dose for 10 days or 3) a 2-day pulsed dose.

Results

Gefitinib treatment resulted in significant tumor growth inhibition (pulsed: 439 ± 93; daily: 404 ± 53; control: 891 ± 174 mm3, P < 0.050) and lower cell density (pulsed: 0.15 ± 0.01, daily: 0.17 ± 0.01, control: 0.24 ± 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but decreased in controls (P > 0.050). Tumor Kps decreased with pulsed treatment but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor fPV increased in both treated groups, decreasing afterwards with pulsed treatment (P > 0.050).

Conclusion

Quantitative MRI can provide a sensitive measure of gefitinib-induced tumor changes, potentially distinguish between treatment regimens, and may be useful for determining optimal treatment scheduling for enhancing chemotherapy delivery. J. Magn. Reson. Imaging 2009;29:1071–1079. © 2009 Wiley-Liss, Inc.

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