Complete microscale profiling of tumor microangiogenesis: a microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization

Abstract

Complete profiling would substantially facilitate the fundamental understanding of tumor angiogenesis and of possible anti-angiogenesis cancer treatments. We developed an integrated synchrotron-based methodology with excellent performances: detection of very small vessels by high spatial resolution (~1 μm) and nanoparticle contrast enhancement, in vivo dynamics investigations with high temporal resolution (~1 ms), and three-dimensional quantitative morphology parametrization by computer tracing. The smallest (3-10 μm) microvessels were found to constitute >80% of the tumor vasculature and exhibit many structural anomalies. Practical applications are presented, including vessel microanalysis in xenografted tumors, monitoring the effects of anti-angiogenetic agents and in vivo detection of tumor vascular rheological properties.