Abstract 386: Real-time noninvasive optical imaging of angiogenesis and vasculogenesis inhibition and normalization

Abstract

Abstract We have developed and optimized non-invasive in vivo imaging to continuously visualize and characterize tumor angiogenesis and vascular response to anticancer therapies in real time in live mice. Tumor vessels could be monitored longitudinally undergoing vasculogenesis and angiogenesis the same mouse. Morphometric changes of the same vessel prior to and after drug treatment were captured with high resolution. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were imaged. The multi-channel imaging capability of the OV100 small animal imaging system (Olympus) enabled visualization of the functional integrity (permeability) of tumor vessels before and after anti-angiogenic therapies using the near-infrared blood pool reagent Angiosense750. We observed real-time tumor vessel normalization as demonstrated by significantly reduced leakiness and subsequent improved delivery of BODPY-Paclitaxel upon administration of low-dose and short-term anti-angiogenic therapy. Further, alterations in Angiosense750 tumor retention in response to different treatments were confirmed and quantified using noninvasive fluorescent molecular tomography (VisEN FMT). Histological, and immunofluorescence staining (CD31, lectin, SMA, NG2) along with confocal microscopy, confirmed the in vivo imaging observations. Thus, imaging is a powerful tool for investigating tumor angiogenic progression and for preclinical drug screening of anti-angiogenic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 386.