title: In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts.
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.
authors: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors: Devin R
authors: DR
authors: McCormack
authors: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors: Alex J
authors: AJ
authors: Walsh
authors: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors: Wesley
authors: W
authors: Sit
authors: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232 USA ; Department of Medicine, Vanderbilt University, Nashville, TN 37232 USA ; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
authors: Carlos L
authors: CL
authors: Arteaga
authors: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232 USA ; Department of Cell and Developmental Biology, Vanderbilt University, Nashville TN 37232, USA.
authors: Jin
authors: J
authors: Chen
authors: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232 USA ; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
authors: Rebecca S
authors: RS
authors: Cook
authors: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors: Melissa C
authors: MC
authors: Skala
keywords: (110.4234) Multispectral and hyperspectral imaging; (170.1470) Blood or tissue constituent monitoring; (170.3880) Medical and biological imaging