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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 7 — Jul. 1, 2014
  • pp: 2247–2261

In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts

Devin R. McCormack, Alex J. Walsh, Wesley Sit, Carlos L. Arteaga, Jin Chen, Rebecca S. Cook, and Melissa C. Skala  »View Author Affiliations

Biomedical Optics Express, Vol. 5, Issue 7, pp. 2247-2261 (2014)

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HER2-amplified (HER2 + ) breast cancers are treated with the anti-HER2 monoclonal antibody trastuzumab. Although trastuzumab reduces production of the angiogenic factor VEGF in HER2 + tumors, the acute and sustained effects of trastuzumab on the tumor vasculature are not understood fully, particularly in trastuzumab-resistant tumors. We used mouse models of trastuzumab sensitive and trastuzumab-resistant HER2 + breast cancers to measure dynamic changes in tumor microvessel density and hemoglobin oxygenation (sO2) in vivo using quantitative hyperspectral imaging at 2, 5, 9, and 14 days after antibody treatment. Further analysis quantified the distribution of microvessels into low and high oxygenation groups, and monitored changes in these distributions with trastuzumab treatment. Gold standard immunohistochemistry was performed to validate complementary markers of tumor cell and vascular response to treatment. Trastuzumab treatment in both responsive and resistant tumors resulted in decreased sO2 5 days after initial treatment when compared to IgG-treated controls (p<0.05). Importantly, responsive tumors showed significantly higher vessel density and significantly lower sO2 than all other groups at 5 days post-treatment (p<0.05). Distribution analysis of vessel sO2 showed a significant (p<0.05) shift of highly oxygenated vessels towards lower oxygenation over the time-course in both trastuzumab-treated responsive and resistant tumors. This study suggests that longitudinal hyperspectral imaging of microvessel sO2 and density could distinguish trastuzumab-responsive from trastuzumab-resistant tumors, a finding that could be exploited in the post-neoadjuvant setting to guide post-surgical treatment decisions.

© 2014 Optical Society of America

OCIS Codes
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(110.4234) Imaging systems : Multispectral and hyperspectral imaging

ToC Category:
Optics in Cancer Research

Original Manuscript: April 17, 2014
Revised Manuscript: June 7, 2014
Manuscript Accepted: June 10, 2014
Published: June 16, 2014

Devin R. McCormack, Alex J. Walsh, Wesley Sit, Carlos L. Arteaga, Jin Chen, Rebecca S. Cook, and Melissa C. Skala, "In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts," Biomed. Opt. Express 5, 2247-2261 (2014)

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