Cardiovascular molecular imaging: focus on clinical translation.
Cardiovascular molecular imaging: focus on clinical translation.
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DOI：
10.1161/circulationaha.109.916338
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发表时间：
2011-02-01
期刊：
影响因子：
37.8
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
Chen IY;Wu JC
在过去的几十年里，由于分子生物学研究的迅速发展，对心血管疾病分子基础的认识出现了爆炸式增长。在基因组、转录和蛋白质组水平上对疾病发病机制的更好理解已经导致发现了用于预防、诊断和治疗心血管疾病的有前景的实验策略。不幸的是，这些策略中只有一小部分在临床前和临床试验的严格考验中幸存下来，成为治疗上有用的。此外，即使这些成功的策略也必须忍受从实验室到床边的长期翻译过程，部分原因是缺乏直接询问患者分子事件的工具。发展非侵入性成像技术以可视化患者分子变化的强大推动力催生了分子成像领域。1，2分子成像起源于核医学，其中放射性标记的成像探针被注射到活体中以评估不同器官系统的功能。与描绘心血管系统解剖结构（例如冠状动脉管腔直径）的传统诊断成像技术（例如放射照相术和计算机断层扫描[CT]）不同，分子成像技术已被设计和验证用于研究可能构成疾病过程的小规模分子事件（例如基因表达）。分子成像的复杂性在于对分子靶向的要求，分子靶向的设计需要对成像探针的药代动力学以及它如何与分子靶点相互作用有扎实的理解。当靶点被证明是一种生物标志物时，分子成像就成为一种有价值的工具，可用于在临床表现之前检测疾病、对疾病严重程度进行分层、预测疾病进展、监测治疗效果和诊断疾病。在充分实现个性化医疗的真正潜力之前，必须应对这些挑战。3分子影像学已经取得了重大进展，使其在许多领域成为临床现实。在过去的20年里，小动物成像技术的进步对其发展起到了重要作用，包括荧光成像（FI）、生物发光成像（BLI）、超声、微型正电子发射断层扫描（micro-PET）、微型单光子发射计算机断层扫描（microSPECT）、高场小动物磁共振成像（MRI）和微型计算机断层扫描（microCT;图1A）。一个平行的发展是构建复杂的成像探针，对各种分子靶标具有高特异性。这些成像系统和探针的使用促进了分子成像技术在动物模型中的验证。通过使用临床版本的小动物扫描仪或专门为临床翻译开发的特殊成像平台，正在将这些技术持续转化为临床竞技场。广泛的令人兴奋的心血管分子成像应用现在已经开发和审查以前。1，4，5在简要概述了分子成像方法的基本原理后，本综述将重点介绍动脉粥样硬化，心力衰竭和干细胞治疗领域的最新进展。文章最后将讨论分子影像学在临床竞技场的未来前景，以及在后基因组时代的分子影像学的未来发展方向。
The past few decades have seen an explosion in the knowledge of the molecular basis of cardiovascular diseases owing to rapid advances in molecular biology research. An improved understanding of disease pathogenesis at the genomic, transcriptional, and proteomic levels has led to the discovery of promising experimental strategies for the prevention, diagnosis, and treatment of cardiovascular disease. Unfortunately, only a minute number of these strategies have survived the rigors of preclinical and clinical trials to become therapeutically useful. Furthermore, even these successful strategies must endure a prolonged process of translation from bench to bedside, partially owing to the lack of tools to directly interrogate the molecular events in patients. The strong impetus to develop noninvasive imaging techniques to visualize molecular changes in patients has given birth to the field of molecular imaging. 1, 2 Molecular imaging has its roots in nuclear medicine, in which radiolabeled imaging probes are injected into living subjects to assess the functionality of different organ systems. Unlike conventional diagnostic imaging techniques (eg, radiography and computed tomography [CT]) that delineate the anatomy of the cardiovascular system (eg, coronary luminal diameter), molecular imaging techniques have been designed and validated to study much smaller-scale molecular events (eg, gene expression) that may underlie disease processes. The complexity of molecular imaging lies in the requirement for molecular targeting, the design of which requires a solid understanding of the pharmacokinetics of the imaging probe and how it interacts with the molecular target. When the target is proven to be a biomarker, molecular imaging becomes a valuable tool for detecting disease before its clinical manifestation, stratifying disease severity, predicting disease progression, monitoring treatment efficacy, and prognosticating disease. These challenges must be met before the true potential of personalized medicine can be fully realized. 3 Significant advances have been made in molecular imaging to make it a clinical reality in many areas. Instrumental in its development has been the advancement of small-animal imaging technologies over the past 2 decades, including fluorescence imaging (FI), bioluminescence imaging (BLI), ultrasound, micro-positron emission tomography (micro-PET), micro–single photon emission computed tomography (microSPECT), high-field small animal magnetic resonance imaging (MRI), and micro–computed tomography (microCT; Figure 1A). A parallel development has been the construction of sophisticated imaging probes with high specificity for various molecular targets. The use of these imaging systems and probes has facilitated the validation of molecular imaging techniques in animal models. Ongoing translation of these techniques into the clinical arena is being achieved by use of either clinical versions of small-animal scanners or special imaging platforms specifically developed for clinical translation. A wide range of exciting cardiovascular molecular imaging applications have now been developed and reviewed previously. 1, 4, 5 After a brief overview of the fundamentals of molecular imaging approaches, the present review will focus on the latest advances in the areas of atherosclerosis, heart failure, and stem cell therapy. The article will conclude with discussions on the future prospects of molecular imaging in the clinical arena, as well as future directions that will shape molecular imaging in the postgenomics era.