OSA's Digital Library

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)
http://dx.doi.org/10.1364/BOE.5.002247


View Full Text Article

Enhanced HTML    Acrobat PDF (1522 KB)





Browse Journals / Lookup Meetings

Browse by Journal and Year


   


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools

Share
Citations

Abstract

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

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

Citation
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)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-5-7-2247


Sort:  Author  |  Year  |  Journal  |  Reset  

References

  1. R. Siegel, D. Naishadham, and A. Jemal, Cancer Statistics 2013, 11–30 (2013) (doi:10.3322/caac.21166.).
  2. D. J. Slamon, W. Godolphin, L. A. Jones, J. A. Holt, S. G. Wong, D. E. Keith, W. J. Levin, S. G. Stuart, J. Udove, A. Ullrich, and et, “Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer,” Science244(4905), 707–712 (1989). [CrossRef] [PubMed]
  3. J. S. Ross and J. A. Fletcher, “The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy,” Stem Cells16(6), 413–428 (1998). [CrossRef] [PubMed]
  4. M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005). [CrossRef] [PubMed]
  5. C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, D. J. Slamon, M. Murphy, W. F. Novotny, M. Burchmore, S. Shak, S. J. Stewart, and M. Press, “Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer,” J. Clin. Oncol.20(3), 719–726 (2002). [CrossRef] [PubMed]
  6. Y. Izumi, L. Xu, E. di Tomaso, D. Fukumura, and R. K. Jain, “Tumour biology: herceptin acts as an anti-angiogenic cocktail,” Nature416(6878), 279–280 (2002). [CrossRef] [PubMed]
  7. R. K. Jain, “Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy,” Science307(5706), 58–62 (2005). [CrossRef] [PubMed]
  8. M. W. Dewhirst, “Relationships between cycling hypoxia, HIF-1, angiogenesis and oxidative stress,” Radiat. Res.172(6), 653–665 (2009). [CrossRef] [PubMed]
  9. C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, D. J. Slamon, M. Murphy, W. F. Novotny, M. Burchmore, S. Shak, S. J. Stewart, and M. Press, “Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer,” J. Clin. Oncol.20(3), 719–726 (2002). [CrossRef] [PubMed]
  10. G. Valabrega, F. Montemurro, and M. Aglietta, “Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer,” Ann. Oncol.18(6), 977–984 (2007). [CrossRef] [PubMed]
  11. G. Shen, H. Huang, A. Zhang, T. Zhao, S. Hu, L. Cheng, J. Liu, W. Xiao, B. Ling, Q. Wu, L. Song, and W. Wei, “In vivo activity of novel anti-ErbB2 antibody chA21 alone and with Paclitaxel or Trastuzumab in breast and ovarian cancer xenograft models,” Cancer Immunol. Immunother.60(3), 339–348 (2011). [CrossRef] [PubMed]
  12. M. E. Hardee, R. J. Eapen, Z. N. Rabbani, M. R. Dreher, J. Marks, K. L. Blackwell, and M. W. Dewhirst, “Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors,” Cancer Chemother. Pharmacol.63(2), 219–228 (2009). [CrossRef] [PubMed]
  13. C. Shah, T. W. Miller, S. K. Wyatt, E. T. McKinley, M. G. Olivares, V. Sanchez, D. D. Nolting, J. R. Buck, P. Zhao, M. S. Ansari, R. M. Baldwin, J. C. Gore, R. Schiff, C. L. Arteaga, and H. C. Manning, “Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer,” Clin. Cancer Res.15(14), 4712–4721 (2009). [CrossRef] [PubMed]
  14. C. V. Pastuskovas, E. E. Mundo, S. P. Williams, T. K. Nayak, J. Ho, S. Ulufatu, S. Clark, S. Ross, E. Cheng, K. Parsons-Reponte, G. Cain, M. Van Hoy, N. Majidy, S. Bheddah, J. dela Cruz Chuh, K. R. Kozak, N. Lewin-Koh, P. Nauka, D. Bumbaca, M. Sliwkowski, J. Tibbitts, F. P. Theil, P. J. Fielder, L. A. Khawli, and C. A. Boswell, “Effects of anti-VEGF on pharmacokinetics, biodistribution, and tumor penetration of trastuzumab in a preclinical breast cancer model,” Mol. Cancer Ther.11(3), 752–762 (2012). [CrossRef] [PubMed]
  15. S. H. Park, W. K. Moon, N. Cho, J. M. Chang, S.-A. Im, I. A. Park, K. W. Kang, W. Han, and D.-Y. Noh, “Comparison of diffusion-weighted MR imaging and FDG PET/CT to predict pathological complete response to neoadjuvant chemotherapy in patients with breast cancer,” Eur. Radiol.22(1), 18–25 (2012). [CrossRef] [PubMed]
  16. J. F. De Los Santos, A. Cantor, K. D. Amos, A. Forero, M. Golshan, J. K. Horton, C. A. Hudis, N. M. Hylton, K. McGuire, F. Meric-Bernstam, I. M. Meszoely, R. Nanda, and E. S. Hwang, “Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017,” Cancer119(10), 1776–1783 (2013). [CrossRef] [PubMed]
  17. H. Degani, M. Chetrit-Dadiani, L. Bogin, and E. Furman-Haran, “Magnetic resonance imaging of tumor vasculature,” Thromb. Haemost.89(1), 25–33 (2003). [PubMed]
  18. D. B. Jakubowski, A. E. Cerussi, F. Bevilacqua, N. Shah, D. Hsiang, J. Butler, and B. J. Tromberg, “Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study,” J. Biomed. Opt.9(1), 230–238 (2004). [CrossRef] [PubMed]
  19. A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.104(10), 4014–4019 (2007). [CrossRef] [PubMed]
  20. B. S. Sorg, B. J. Moeller, O. Donovan, Y. Cao, and M. W. Dewhirst, “Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development,” J. Biomed. Opt.10(4), 044004 (2005). [CrossRef] [PubMed]
  21. G. M. Palmer, A. N. Fontanella, S. Shan, G. Hanna, G. Zhang, C. L. Fraser, and M. W. Dewhirst, “In vivo optical molecular imaging and analysis in mice using dorsal window chamber models applied to hypoxia, vasculature and fluorescent reporters,” Nat. Protoc.6(9), 1355–1366 (2011). [CrossRef] [PubMed]
  22. R. D. Shonat, E. S. Wachman, W. Niu, A. P. Koretsky, and D. L. Farkas, “Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope,” pp. 1223–1231 (1997).
  23. J. A. Lee, N. M. Biel, R. T. Kozikowski, D. W. Siemann, and B. S. Sorg, “In vivo spectral and fluorescence microscopy comparison of microvascular function after treatment with OXi4503, Sunitinib and their combination in Caki-2 tumors,” Biomed. Opt. Express5(6), 1965 (2014). [CrossRef]
  24. K. J. Zuzak, M. D. Schaeberle, E. N. Lewis, and I. W. Levin, “Visible Reflectance Hyperspectral Imaging: Characterization of a Noninvasive, in Vivo System for Determining Tissue Perfusion,” Anal. Chem.74(9), 2021–2028 (2002). [CrossRef] [PubMed]
  25. A. N. Fontanella, “Novel Methods of Optical Data Analysis to Assess Radiation Responses in the Tumor Microenvironment,” Duke University (2013).
  26. B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009). [CrossRef] [PubMed]
  27. C. A. Ritter, M. Perez-Torres, C. Rinehart, M. Guix, T. Dugger, J. A. Engelman, and C. L. Arteaga, “Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network,” Clin. Cancer Res.13(16), 4909–4919 (2007). [CrossRef] [PubMed]
  28. H. C. Hendargo, R. Estrada, S. J. Chiu, C. Tomasi, S. Farsiu, and J. A. Izatt, “Automated non-rigid registration and mosaicing for robust imaging of distinct retinal capillary beds using speckle variance optical coherence tomography,” Biomed. Opt. Express4(6), 803–821 (2013). [CrossRef] [PubMed]
  29. P. Santago and H. D. Gage, “Quantification of MR brain images by mixture density and partial volume modeling,” IEEE Trans. Med. Imaging12(3), 566–574 (1993). [CrossRef] [PubMed]
  30. H. Akaike, “A new look at the statistical model identification,” IEEE Trans. Automat. Contr.19(6), 716–723 (1974). [CrossRef]
  31. A. J. Walsh, R. S. Cook, H. C. Manning, D. J. Hicks, A. Lafontant, C. L. Arteaga, and M. C. Skala, “Optical metabolic imaging identifies glycolytic levels, subtypes, and early-treatment response in breast cancer,” Cancer Res.73(20), 6164–6174 (2013). [CrossRef] [PubMed]
  32. G. Brockhoff, B. Heckel, E. Schmidt-Bruecken, M. Plander, F. Hofstaedter, A. Vollmann, and S. Diermeier, “Differential impact of Cetuximab, Pertuzumab and Trastuzumab on BT474 and SK-BR-3 breast cancer cell proliferation,” Cell Prolif.40(4), 488–507 (2007). [CrossRef] [PubMed]
  33. G. D. Yancopoulos, S. Davis, N. W. Gale, J. S. Rudge, S. J. Wiegand, and J. Holash, “Vascular-specific growth factors and blood vessel formation,” Nature407(6801), 242–248 (2000). [CrossRef] [PubMed]
  34. J. O. A. Forsythe, B. Jiang, N. V Iyer, F. Agani, and S. W. Leung, “Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1” (1996).
  35. M. Potente, H. Gerhardt, and P. Carmeliet, “Basic and therapeutic aspects of angiogenesis,” Cell146(6), 873–887 (2011). [CrossRef] [PubMed]
  36. K. Vishwanath, H. Yuan, W. T. Barry, M. W. Dewhirst, and N. Ramanujam, “Using optical spectroscopy to longitudinally monitor physiological changes within solid tumors,” Neoplasia11(9), 889–900 (2009). [PubMed]
  37. T. D. O’Sullivan, A. Leproux, J.-H. Chen, S. Bahri, A. Matlock, D. Roblyer, C. E. McLaren, W.-P. Chen, A. E. Cerussi, M. Y. Su, and B. J. Tromberg, “Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy,” Breast Cancer Res.15(1), R14 (2013). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited