A ''smart'' magnetic resonance imaging agent that reports on specific enzymatic activity
A ''smart'' magnetic resonance imaging agent that reports on specific enzymatic activity
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DOI：
10.1002/anie.199707261
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发表时间：
1997-04-18
影响因子：
16.6
通讯作者：
Meade, TJ
中科院分区：
文献类型：
--
作者：
Moats, RA;Fraser, SE;Meade, TJ
现代光学显微镜技术与荧光指示剂化合物相结合，通过检测完整细胞和组织的生理学，彻底改变了生物结构，功能和发育的研究！例如，荧光染料经常被注射到透明胚胎的细胞中以追踪其直系后代的命运。结合Ca 2+后改变其强度或波长的荧光染料提供了对细胞生理学的见解。此外，荧光底物染料可用于通过将β-半乳糖苷酶基因与感兴趣的基因的调节结构域融合来跟踪特定基因的激活。然而，光学技术，从视频显微镜到激光扫描共聚焦显微镜，由于光散射和未校正的光学，在生物组织的最外层100 μ m中效果最好。生物结构的磁共振成像（MRI）提供了一种替代光学显微镜的方法，可以规避这些限制。并且最近的分析证明了在细胞分辨率（约10 μ m）下的真实三维MR成像的可行性。r31为了利用MRI的力量进行生物学研究，必须开发类似于光学显微镜中使用的荧光指示剂染料的造影剂。在这里，我们描述了一类创新的酶促反应或“智能”MRI造影剂的第一个成员，该造影剂被设计用于报告细胞和器官的代谢状态，并以获得的MRI图像的形式传输此信息。
Modern optical microscopy techniques combined with fluorescent indicator compounds have revolutionized studies of biological structure, function, and development by allowing the physiology of intact cells and tissues to be assayed!’] For example, fluorescent dyes are often injected into celIs of transparent embryos in order to follow the fate of their lineal descendants. Fluorescent dyes that change their intensity or wavelength upon binding Ca2+ have afforded insights into cell physiology. Further, fluorogenic substrate dyes can be used to follow the activation of a specific gene by fusing the b-galactosidase gene with the gene of interest’s regulatory domain. However, optical techniques, ranging from video-microscopy to laser scanning confocal microscopy, work best in the outermost 100 pm of biological tissue because of light scattering and uncorrected opticalMagnetic resonance imaging (MRI) of biological structures offers an alternative to light microscopy that can circumvent these limitations, and recent analyses demonstrate the feasibility of true three-dimensional MR imaging at cellular resolution (about 10pm). r31 In order to exploit the power of MRI for biological studies, contrast agents that are analogous to fluorescent indicator dyes used in light microscopy must be developed. Here, we describe the first member of an innovative new class of enzymatically responsive or “smart” MRI contrast agents that has been designed to report on the metabolic state of cells and organs and transmit this information in the form of an acquired MRI image.