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 in trastuzumab-resistant tumors. Hyperspectral imaging is used to quantify microvessel density and hemoglobin oxygenation (sO2) of trastuzumab responsive and resistant breast cancers after antibody treatment in vivo. Microvessel dynamics are monitored over a 14 day time-course. Immunohistochemistry validates 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). 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.