On the validity of the first-pass binding model for quantitative ultrasound molecular imaging: Comparison between BR55 and Sonovue

Cancer growth requires angiogenesis; imaging of angiogenesis may thus improve cancer diagnostics and therapy monitoring. Dynamic contrast enhanced ultrasound (DCE-US) permits imaging angiogenesis at the molecular level by using novel targeted ultrasound contrast agents (tUCA). These agents consist of functionalized microbubbles obtained by engineering their shell with targeting ligands able to bind specific biomarkers, over-expressed in tumor angiogenic vasculature. Quantification of binding may thus provide an indirect way of quantifying angiogenesis. Recently, we proposed the first-pass binding (FPB) model to describe the binding kinetics of tUCA. Fitting DCE-US time-intensity curves (TICs) by the FPB model enables quantification of binding by the estimation of the binding rate Kb. After showing the feasibility of the method for angiogenesis imaging in prostate-tumor bearing rats, and performing a preliminary validation for anti-angiogenesis therapy monitoring in colon cancer-bearing mice, in this work we investigated the validity of the proposed model by comparing Kb estimates in rats injected with non-targeted UCAs (Sonovue) and tUCAs (BR55). Significantly lower values of Kb were found for Sonovue compared to BR55, with no significant difference between cancer and healthy prostate for Sonovue