Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems
Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems
复制标题
DOI：
10.1021/acssensors.0c00322
复制
发表时间：
2020-06-26
期刊：
影响因子：
8.9
通讯作者：
Jasanoff, Alan
中科院分区：
文献类型：
--
作者：
Barandov, Ali;Ghosh, Souparno;Jasanoff, Alan
由于一氧化氮的物理化学性质和现有成像方法和探针的局限性，生物系统中一氧化氮(NO)的检测是具有挑战性的。磁共振成像(MRI)可用于研究具有高时空分辨率的活体组织中的NO，但仍需要有效地使MRI对生物NO产生敏感的化学试剂。为了开发合适的探针，我们研究了NO与一系列不同氧化态和分子结构的锰络合物之间的相互作用。其中，N，N‘-(1，2-phenylene)bis(5-fluoro-2-hydroxybenzamide)与锰(III)的络合物在体外加入NO释放化学物质后，显示出良好的纵向弛豫度变化，同时还保持了对其他生物相关活性氮和氧物种的选择性，使其成为适合于T-1加权磁共振成像的无响应性造影剂。当负载该化合物时，异位表达一氧化氮合酶(NOS)亚型的细胞显示，与对照细胞相比，MRI信号降低了20%以上，并且对NOS抑制或钙依赖激活也有反应。该传感器还可以在体内检测抗原刺激的巨噬细胞和神经炎症大鼠模型中的内源性NOS活性。鉴于NO及其相关的反应氮物种在许多生理和病理过程中的关键作用，基于新探针的MRI方法可能对活体对象中NO相关信号的研究具有广泛的益处。
Detection of nitric oxide (NO) in biological systems is challenging due to both physicochemical properties of NO and limitations of current imaging modalities and probes. Magnetic resonance imaging (MRI) could be applied for studying NO in living tissue with high spatiotemporal resolution, but there is still a need for chemical agents that effectively sensitize MRI to biological NO production. To develop a suitable probe, we studied the interactions between NO and a library of manganese complexes with various oxidation states and molecular structures. Among this set, the manganese(III) complex with N,N'-(1,2-phenylene)bis(5-fluoro-2-hydroxybenzamide) showed favorable changes in longitudinal relaxivity upon addition of NO-releasing chemicals in vitro while also maintaining selectivity against other biologically relevant reactive nitrogen and oxygen species, making it a suitable NO-responsive contrast agent for T-1-weighted MRI. When loaded with this compound, cells ectopically expressing nitric oxide synthase (NOS) isoforms showed MRI signal decreases of over 20% compared to control cells and were also responsive to NOS inhibition or calcium-dependent activation. The sensor could also detect endogenous NOS activity in antigen-stimulated macrophages and in a rat model of neuroinflammation in vivo. Given the key role of NO and associated reactive nitrogen species in numerous physiological and pathological processes, MRI approaches based on the new probe could be broadly beneficial for studies of NO-related signaling in living subjects.