State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, PR China.
Acc Chem Res. 2012 Oct 16;45(10):1817-27. doi: 10.1021/ar300150c. Epub 2012 Sep 5.
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.
X 射线计算机断层扫描（CT）是现代医学中最强大的非侵入性诊断成像技术之一。然而，临床上用作 CT 造影剂的碘化物分子在体内的循环时间相对较短，这极大地限制了该技术在靶向成像和血管造影中的应用。此外，这些造影剂的使用可能会带来不良反应。例如，由于碘的对比度效果较低，成年患者通常会接受约 70 毫升的碘造影剂（350mgI/mL）。如此大剂量的这些造影剂快速经肾脏清除可能会导致严重的不良反应。此外，一些患者对碘过敏。因此，生物医学研究人员投入了大量精力来解决这些问题。在过去的十年中，纳米科学的进步为成像创造了新的范例。纳米材料的独特性质，例如其延长的循环半衰期、在肿瘤部位的被动积累、易于表面修饰以及将多种不同功能整合到单个颗粒中，使它们在体内应用中具有优势。然而，由于制备具有成本效益、优异生物相容性、高对比度效果、长体内循环时间和在生理环境中长期胶体稳定性的纳米颗粒 CT 造影剂的挑战，纳米材料在 CT 成像中的应用研究远远落后于其在 MRI 和荧光成像等其他成像技术中的应用。本综述回顾了我们在设计和体内应用纳米颗粒 CT 造影剂方面的最新工作。通过根据 X 射线成像的基本原理优化纳米颗粒中的造影元素，并采用我们和其他人开发的表面工程方法，我们合成了几种具有优异成像性能的纳米颗粒 CT 造影剂。例如，与目前可用的 CT 造影剂相比，新型基于 Yb 的纳米颗粒造影剂在正常工作条件下提供了增强的对比度效果。为了应对特殊情况，我们将具有很大差异的 K 边值的 Ba 和 Yb 整合到一个单一的颗粒中，得到了第一个二元造影剂的例子。与碘造影剂相比，该造影剂在不同电压下显示出更高的对比度，非常适合各种患者的诊断成像。由于其延长的体内循环时间和极低的毒性，这些造影剂可用于血管造影。
