Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA; Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA; Department of Nuclear Science & Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
Free Radic Biol Med. 2022 Oct;191:241-248. doi: 10.1016/j.freeradbiomed.2022.08.042. Epub 2022 Sep 6.
Wide field measurements of nitric oxide (NO) signaling could help understand and diagnose the many physiological processes in which NO plays a key role. Magnetic resonance imaging (MRI) can support particularly powerful approaches for this purpose if equipped with molecular probes sensitized to NO and NO-associated targets. In this review, we discuss the development of MRI-detectable probes that could enable studies of nitrergic signaling in animals and potentially human subjects. Major families of probes include contrast agents designed to capture and report integrated NO levels directly, as well as molecules that respond to or emulate the activity of nitric oxide synthase enzymes. For each group, we outline the relevant molecular mechanisms and discuss results that have been obtained in vitro and in animals. The most promising in vivo data described to date have been acquired using NO capture-based relaxation agents and using engineered nitric oxide synthases that provide hemodynamic readouts of NO signaling pathway activation. These advances establish a beachhead for ongoing efforts to improve the sensitivity, specificity, and clinical applicability of NO-related molecular MRI technology.
宽场测量一氧化氮（NO）信号可以帮助理解和诊断 NO 发挥关键作用的许多生理过程。如果配备了对 NO 及其相关靶标敏感的分子探针，磁共振成像（MRI）可以为此提供特别强大的方法。在这篇综述中，我们讨论了可用于研究动物甚至人类中氮能信号的 MRI 可检测探针的开发。主要的探针家族包括旨在直接捕获和报告综合 NO 水平的对比剂，以及对一氧化氮合酶（NOS）酶的活性做出响应或模拟其活性的分子。对于每一组，我们概述了相关的分子机制，并讨论了在体外和动物中获得的结果。迄今为止，最有前途的体内数据是使用基于 NO 捕获的弛豫剂和使用提供 NO 信号通路激活的血液动力学读数的工程化一氧化氮合酶获得的。这些进展为提高与 NO 相关的分子 MRI 技术的灵敏度、特异性和临床适用性的持续努力奠定了基础。
