Circulating and imaging markers for angiogenesis

Abstract

Abundant preclinical and indirect clinical data have for several decades convincingly supported the notion that anti-angiogenesis is an effective strategy for the inhibition of tumor growth. The recent success achieved in patients with metastatic colon carcinoma using a neutralizing antibody directed against vascular endothelial growth factor (VEGF) has translated preclinical optimism into a clinical reality.With this transformation in the field of angiogenesis has come a need for reliable surrogate markers. A surrogate marker by definition serves as a substitute for the underlying process in question, and in the case of angiogenesis, microvessel density (usually in so-called "hot-spots") has until now been the most widely used parameter. However, this parameter is more akin to a static "snapshot" and does not lend itself either to the dynamic in situ assessment of the status of the tumor microvasculature or to the molecular factors that regulate its growth and involution. This has led to an acute need for developing circulating and imaging markers of angiogenesis that can be monitored in vivo at repeated intervals in large number of patients with a variety of tumors in a non-invasive manner. Such markers of angiogenesis are the subject of this review.

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

“…Both cerebral blood volume and vessel size index measurements are derived from susceptibility-contrast MRI, but the relationship between brain tumor angiogenesis and susceptibility-induced contrast is not well understood. It has been shown that abnormal tumor vessel morphology can profoundly affect susceptibility-induced contrast (Pathak et al, 2003), and that computational models incorporating the actual vascular structure are required to elucidate this complex relationship (Kiselev, 2001;Pathak et al, 2003Pathak et al, , 2008a. This is now possible with the mMRI data acquired in this work and the recent development of a computational model of MRI contrast known as the finite perturber method (Pathak et al, 2008c).…”

Hyperpolarized 13C Spectroscopy Detects Early Changes in Tumor Vasculature and Metabolism after VEGF Neutralization

“…The rapid adoption of bevacizumab in the clinic has led to an urgent need to develop biomarkers that can select patients that will best respond to the therapy, direct drug dose, and sensitively detect response to treatment (15)(16)(17); such biomarkers have remained elusive (14). Dynamic contrast agent-enhanced MRI (DCE-MRI) of the tumor vasculature has proved promising in this regard (17), with patients whose tumors undergo a 50% or greater reduction in contrast agent uptake within the first cycle of treatment usually attaining stable or better disease (18).…”

Multiexposure laser speckle contrast imaging of the angiogenic microenvironment

“…11 Consequently, there exists a significant need for noninvasive in vivo imaging methods capable of sequentially assessing angiogenesis over a period of days, in a variety of disease models. 12 This would require a high contrast-to-noise ratio (CNR) technique that is sensitive to both, low-flow neovasculature as well as higher flow normal vasculature. Conventional LSCI, which uses a spatial windowing scheme for contrast calculation, cannot distinguish microvessels due to its limited spatial resolution.…”