Non-invasive assessment of tumor neovasculature: techniques and clinical applications

The ability to induce and sustain angiogenesis is regarded as one of the hallmarks of cancer growth and metastasis. Marked advances in understanding vascular physiology and mechanisms of angiogenesis have led to the development of vascularly-targeted anti-cancer therapies. Two broad subclasses of agents are in clinical use currently: those with anti-angiogenic activity (i.e. those that target angiogenic pathways) and those that have direct cytotoxic activity against proliferating endothelial cells (i.e. vascular disruptive agents (VDAs)). This article reviews the various imaging modalities, including magnetic resonance imaging, computed tomography, photon emission imaging (positron emission tomography and single photon emission computed tomography), ultrasound and optical (near-infrared absorption and scattering) techniques that have been used in an attempt to assess the status of tumor neovasculature in vivo. In each case, we describe the basic imaging methodology, methods for image quantification, technical standardization and reproducibility, and current and potential clinical applications for monitoring the status of tumor neovasculature before and during treatment with vascular targeted agents.