Investigations of Antiangiogenic Mechanisms Using Novel Imaging Techniques
Abstract
This study is intended to investigate the physiological effects of anti-angiogenic and anti-tumor treatment at the microcirculatory level with the intent to better understand how the tumor adapts to these treatments, with the aim of formulating more effective treatment modalities based off this knowledge. We have recently had the opportunity to form a collaboration with a research group investigating the effects of microbeam radiation therapy (MRT). Previous studies have shown that MRT induces a strong anti-tumor effect while sparing normal tissue. The mechanisms of this tissue sparing effect are poorly understood, however. Investigation of MRT in the murine window chamber model will not only elucidate the mechanisms of MRT, but will also provide further insight into natural tumor progression and how the tumor may respond to vascular disrupting agents in general. We have employed a number of advanced techniques in the window chamber model to optically observe natural and induced changes in tumor physiology. These advanced imaging modalities have the advantage of being able to facilitate longitudinal, in vivo investigation into the parameters of interest. These include Doppler Optical Coherence Tomography for the measurement of blood flow velocity, Hyperspectral Imaging for the measurement of hemoglobin saturation and hematocrit, and Confocal Imaging for the measurement of 3-D vascular architecture and perfusion. Additionally, novel methods have been developed to molecularly probe the tumor environment. These include Oxygen Sensitive Nanoparticles for the mapping of pO2 and the use of Engineered Cell Lines which express green fluorescent protein under hypoxia. Together, these techniques will allow us to better understand and model the process of tumor growth and response to MRT, eventually leading to a better understanding of how such changes can be exploited to increase the efficacy of combinational therapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2011
- Accession Number
- ADA543571
Entities
People
- Andrew Fontanella
Organizations
- Duke University