Villanueva Flordeliza S
Center for Ultrasound Molecular Imaging and Therapeutics, Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
J Nucl Cardiol. 2008 Jul-Aug;15(4):576-86. doi: 10.1016/j.nuclcard.2008.05.005.
Molecular imaging using probes that specifically home to function- or disease-specific targets is a promising tool for both basic research investigations as well as clinical diagnostics. Ultrasound-based molecular imaging utilizes acoustically active particles (contrast agents) bearing targeting ligands that specifically bind to a molecule of interest. In the presence of an ultrasound field, the bound particles are detectable as a persistent contrast effect during ultrasound imaging. Different types of targeted contrast agents have been reported, most of which share in common the presence of a gas encapsulated by a shell of varying chemical formulation. These agents, or "microbubbles," are typically 2 to 4 mum in diameter, and have a natural resonance frequency that corresponds to the frequencies used in diagnostic echocardiography. This attribute makes it possible to induce microbubble resonance and non-linear oscillation at diagnostic ultrasound frequencies, leading to acoustic emissions from the microbubbles that can be detected as specific signals during two dimensional ultrasound imaging. Targeting ligands that have been attached to microbubbles include monoclonal antibodies, peptides, and the naturally occurring ligands for the receptor of interest, such as vascular endothelial growth factor. Because the contrast agents stay within the intravascular space, they are ideally suited for detection of endothelial epitopes, such as leukocyte adhesion molecules or angiogenesis receptors. Ultrasound molecular imaging with targeted contrast agents has been used to detect inflammation association with ischemia/reperfusion (ischemic memory), cardiac transplant rejection, early atherosclerosis, and angiogenesis. Application to tumor angiogenesis has also been reported using peptides that specifically bind to angiogenic tumor endothelium. Translation of ultrasound molecular imaging to the clinical arena will require optimization of contrast agent design to maximize specific binding, and customization of imaging systems to sensitively detect the binding events.
使用能特异性归巢至功能或疾病特异性靶点的探针进行分子成像，对于基础研究调查和临床诊断而言都是一种很有前景的工具。基于超声的分子成像利用携带靶向配体的声学活性颗粒（造影剂），这些靶向配体可特异性结合感兴趣的分子。在超声场存在的情况下，结合的颗粒在超声成像过程中可作为持续的造影效果被检测到。已经报道了不同类型的靶向造影剂，其中大多数的共同特点是存在被不同化学配方外壳包裹的气体。这些制剂，即“微泡”，直径通常为2至4微米，并且具有与诊断超声心动图中使用的频率相对应的自然共振频率。这一特性使得在诊断超声频率下诱导微泡共振和非线性振荡成为可能，从而导致微泡发出声发射，在二维超声成像过程中可将其检测为特定信号。已连接到微泡上的靶向配体包括单克隆抗体、肽以及感兴趣受体的天然存在的配体，如血管内皮生长因子。由于造影剂停留在血管内空间，它们非常适合检测内皮表位，如白细胞粘附分子或血管生成受体。使用靶向造影剂的超声分子成像已被用于检测与缺血/再灌注相关的炎症（缺血记忆）、心脏移植排斥反应、早期动脉粥样硬化和血管生成。也有报道使用特异性结合血管生成肿瘤内皮的肽将超声分子成像应用于肿瘤血管生成。将超声分子成像转化到临床领域将需要优化造影剂设计以最大化特异性结合，并定制成像系统以灵敏地检测结合事件。
