Imaging techniques used to monitor angiogenesis

Techniques for imaging angiogenesis help physicians understand the progression and monitor the treatment of cancer, atherosclerosis and other diseases. Although researchers use many of these methods only in animal models, they are finding wider use in humans.

James M. Provenzale of Duke University Medical Center in Durham, N.C., has reviewed current methods for imaging angiogenesis, discussing common antiangiogenic therapy classifications and describing categories of contrast agents that are used.

Researchers typically use indirect imaging for angiogenesis analysis in humans. Perfusion MRI has seen application in transepithelial permeability and in cerebral blood volume measurements in liver and brain tumors. Unfortunately, T1-weighted techniques do not allow ready differentiation of permeability values between benign and malignant tumors.

Scientists have used perfusion CT to identify head and neck tumors based on blood flow, blood volume and capillary permeability, as well as to measure the hemodynamic response of rectal cancer to therapy. To a limited extent, groups have applied PET using ¹⁵O water as a tracer to measure perfusion in tumors. Microbubble analysis and other sonographic techniques reveal tumor vascularity with high sensitivity, but the methods are largely unproven in humans. Photoacoustic imaging is another promising technique but is still in the experimental stage.

Direct imaging techniques that target angiogenesis have been used in animals. In microbubble studies, scientists have targeted α_νβ3 integrin, which yields a high signal-to-noise ratio and seems to effectively show vessel development. Others have used paramagnetic nanoparticles directed at α_νβ3 integrin with T1-weighted MRI to reveal vessel proliferation in atherosclerosis and tumor settings. Another MRI technique has monitored incorporation of labeled endothelial precursor cells into tumor vasculature to help measure angiogenesis.

PET with radiotracer-bound antibodies directed against growth factors is another potential monitoring method. Researchers have revealed α_νβ3 integrin distribution with fluorescent probes and have observed expression of fluorescent reporter genes through a window chamber in tumor-implanted mice. MicroCT, although also not applicable to humans, also may yield preclinical data.

The author concludes that these direct imaging methods will likely provide valuable insights into angiogenesis and could help in antiangiogenic agent development even if their use remains confined to animal models. (American Journal of Roentgenology, January 2007, pp. 11-23).