Nanoparticulate X-ray Computed Tomography Contrast Agents: From Design Validation to in Vivo Applications

Abstract

X-ray computed tomography (CT) is one of the most powerful noninvasive diagnostic imaging techniques in modern medicine. Nevertheless, the iodinated molecules used as CT contrast agents in the clinic have relatively short circulation times in vivo, which significantly restrict the applications of this technique in target-specific imaging and angiography. In addition, the use of these agents can present adverse. For example, an adult patient typically receives approximately 70 mL of iodinated agent (350 mg I/mL) because of iodine's low contrast efficacy. Rapid renal clearance of such a large dose of these agents may lead to serious adverse effects. Furthermore, some patients are hypersensitive to iodine. Therefore, biomedical researchers have invested tremendous efforts to address these issues. Over the past decade, advances in nanoscience have created new paradigms for imaging. The unique properties of nanomaterials, such as their prolonged circulating half-life, passive accumulation at the tumor sites, facile surface modification, and integration of multiple diverse functions into a single particle, make them advantageous for in vivo applications. However, research on the utilization of nanomaterials for CT imaging has lagged far behind their applications for other imaging techniques such as MRI and fluorescence imaging because of the challenges in the preparation of cost-effective nanoparticulate CT contrast agents with excellent biocompatibility, high contrast efficacy, long in vivo circulation time, and long-term colloidal stability in physiological environments. This Account reviews our recent work on the design and in vivo applications of nanoparticulate CT contrast agents. By optimizing the contrast elements in the nanoparticles according to the fundamental principles of X-ray imaging and by employing the surface engineering approaches that we and others have developed, we have synthesized several nanoparticulate CT contrast agents with excellent imaging performance. For example, a novel Yb-based nanoparticulate agent provides enhanced contrast efficacy compared to currently available CT contrast agents under normal operating conditions. To deal with special situations, we integrated both Ba and Yb with great differential in K-edge value into a single particle to yield the first example of binary contrast agents. This agent displays much higher contrast than iodinated agents at different voltages and is highly suited to diagnostic imaging of various patients. Because of their prolonged in vivo circulation time and extremely low toxicity, these agents can be used for angiography.