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 T₁-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.

中文翻译：

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生物系统中一氧化氮的分子磁共振成像。

由于一氧化氮的物理化学性质以及当前成像方式和探针的局限性，生物系统中一氧化氮（NO）的检测具有挑战性。磁共振成像（MRI）可以用于以高时空分辨率研究活组织中的NO，但是仍然需要有效使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与具有各种氧化态和分子结构的锰配合物库之间的相互作用。在这组化合物中，与N，N' -（1,2-亚苯基）双（5-氟-2-羟基苯甲酰胺）形成的锰（III）配合物在体外添加释放NO的化学物质时，纵向弛豫度发生了有利变化同时还保持了对其他生物学相关的活性氮和氧物种的选择性，使其成为适用于T ₁加权MRI的NO响应造影剂。当负载这种化合物时，异位表达一氧化氮合酶（NOS）亚型的细胞显示MRI信号与对照细胞相比下降了20％以上，并且对NOS抑制或钙依赖性激活也有反应。该传感器还可以检测抗原刺激的巨噬细胞和体内神经炎症大鼠模型中的内源性NOS活性。。鉴于NO和相关活性氮物种在众多生理和病理过程中的关键作用，基于这种新探针的MRI方法可能对研究活体内NO相关信号具有广泛的优势。