Quantification of the binding kinetics of targeted ultrasound contrast agent for molecular imaging of cancer angiogenesis

Cancer growth requires angiogenesis; imaging of angiogenesis holds thus great potential for improved cancer detection and treatment. In this context, ultrasound molecular imaging permits the visualization of cancer angiogenesis by use of novel targeted contrast agents (tUCA). These consist of ligand-bearing microbubbles designed to specifically bind molecular angiogenic expressions, thus providing selective enhancement especially in the late phase after injection. Discrimination between bound and free microbubbles is crucial to assess the degree of binding and thus to quantify angiogenesis. Currently, binding is mainly assessed by the differential targeted enhancement, i.e., the difference in signal intensity in the late phase before and after the application of a high-pressure destructive pulse. However, this method is not quantitative, and it requires long acquisitions and a high-pressure pulse, which may damage the endothelial tissue. To overcome these limitations, here we propose a new method for quantification of the microbubble binding kinetics by fitting a dedicated compartmental model to the tUCA first-pass. We investigated the feasibility of the method in three prostate tumor-bearing rats. The novel information provided by the proposed method may be combined with the late enhancement analysis to gain deeper insight into tumor angionesis, and thus potentially improve cancer diagnosis and management.