Molecular Magnetic Resonance Imaging with Gd(III)-Based Contrast Agents: Challenges and Key Advances
Molecular Magnetic Resonance Imaging with Gd(III)-Based Contrast Agents: Challenges and Key Advances
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DOI：
10.1021/jacs.9b09149
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发表时间：
2019-10-30
影响因子：
15
通讯作者：
Meade, Thomas J.
中科院分区：
文献类型：
--
作者：
Li, Hao;Meade, Thomas J.
在个性化医学的时代，临床社区越来越关注在细胞和分子水平上理解疾病。磁共振成像(MRI)是获取解剖和功能信息的一种强大的成像手段。但由于其灵敏度较低，限制了其在分子成像领域的应用。为了将磁共振成像的能力扩展到分子成像应用，我们在1997年引入了基于生物响应性Gd(III)的磁共振造影剂(GBCA)。从那时起，世界各地的许多研究小组都开发出了生物响应性GBCA的新例子。这些造影剂在显示基因表达、神经元信号和激素分泌等生物化学过程方面显示出巨大的潜力。它们被设计成在体内有条件地保留或激活，以响应感兴趣的特定生化事件。因此，观察到的MR信号变化可以作为分子事件的读出。这些探头面临的一个重大挑战是如何将它们用于非侵入性诊断和治疗应用。这一视角侧重于生物响应性探针的设计策略，并描述了近年来取得的关键进展，这些进展促进了它们在体内的应用，并最终应用于临床翻译。虽然生物响应剂的领域还处于萌芽阶段，但很明显，今天的许多实验和临床放射学问题的解决方案将被明天的探测器所克服。
In an era of personalized medicine, the clinical community has become increasingly focused on understanding diseases at the cellular and molecular levels. Magnetic resonance imaging (MRI) is a powerful imaging modality for acquiring anatomical and functional information. However, it has limited applications in the field of molecular imaging due to its low sensitivity. To expand the capability of MRI to encompass molecular imaging applications, we introduced bioresponsive Gd(III)-based magnetic resonance contrast agents (GBCAs) in 1997. Since that time, many research groups across the globe have developed new examples of bioresponsive GBCAs. These contrast agents have shown great promise for visualizing several biochemical processes, such as gene expression, neuronal signaling, and hormone secretion. They are designed to be conditionally retained, or activated, in vivo in response to specific biochemical events of interest. As a result, an observed MR signal change can serve as a read-out for molecular events. A significant challenge for these probes is how to utilize them for noninvasive diagnostic and theranostic applications. This Perspective focuses on the design strategies that underlie bioresponsive probes, and describes the key advances made in recent years that are facilitating their application in vivo and ultimately in clinical translation. While the field of bioresponsive agents is embryonic, it is clear that many solutions to the experimental and clinical radiologic problems of today will be overcome by the probes of tomorrow.