Complete microscale profiling of tumor microangiogenesis: a microradiological methodology reveals fundamental aspects...

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.