In cancer therapy, anti-angiogenesis is a promising candidate treatment protocol. The basis for tumor growth is angiogenesis; that is the creation of a blood supply to support the growth tumor cells with oxygen and other nutrients. The use of angiogenesis inhibitors (for example, the humanized monoclonal antibody Bevacizumab, trade name AVASTIN from Genentech, South San Francisco, Calif.) causes blood vessel maturation and regression in tumors. By this mechanism, the growth of a tumor can be stopped or slowed in certain circumstances.
The use of angiogenesis inhibitors results in changes in relative blood volume, permeability and perfusion which can be monitored by magnetic resonance imaging (MRI) techniques. However, there is no clinically evaluated surrogate endpoint for anti-cancer therapy regimens. At present, volumetric measurements, such as measurements of the biggest tumor diameter, are used to determine the response of a patient or experimental animal to the therapy. A volumetric measurement, however, does not appear to be sufficiently reliable and nor does such a measurement provide an early assessment of outcome.
Anti-angiogenic tumor therapies (e.g., with AVASTIN) would benefit from stable and early indicators of therapeutic effectiveness. In this context, dynamic contrast enhanced (DCE) MRI in combination with the administration of diffusible contrast agents has proven promising. Applying pharmacokinetic models to the dynamic MRI data, parameter maps with physiological relevant information like transfer constant (Ktrans), extra-vascular extra-cellular volume fraction (Ve), or vascular volume fraction (Vp) can be calculated. Using user-defined regions-of-interest (ROI), it is possible to calculate and compare quantitative results for specific tissues-of-interest.
The transfer constant Ktrans has shown to be an early marker of biological response of tumor tissue to anti-angiogenic therapy, but reproducibility studies have shown that changes appear to be obscured by poor reproducibility statistics. Only changes in the range of 50% are considered to be significant in isolation as a reliable assessment of therapeutic effectiveness.