Simultaneous molecular imaging of redox reactions monitored by overhauser-enhanced MRI with 14N- and 15N-labeled nitroxyl radicals
Simultaneous molecular imaging of redox reactions monitored by overhauser-enhanced MRI with 14N- and 15N-labeled nitroxyl radicals
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DOI：
10.1073/pnas.0510670103
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发表时间：
2006-01-31
影响因子：
11.1
通讯作者：
Nagai, M
中科院分区：
文献类型：
--
作者：
Utsumi, H;Yamada, K;Nagai, M
MRI在疾病诊断中具有重要的临床应用价值，并将成为评估基因工程动物表型变化的有力工具。Overhauser增强MRI（OMRI）是一种双共振技术，通过利用Overhauser效应增强水质子信号强度来创建小动物体内自由基分布的图像。几项研究已经证明了通过使用低频电子自旋共振（ESR）光谱/成像和硝酰基自由基对小动物中活性氧产生的无创评估。在体内ESR信号强度的硝酰基自由基注射后随时间的推移而减少，并通过活性氧增强减少，在氧化性疾病模型中产生的位点特异性的方式。在这项研究中，我们显示了图像的硝酰基自由基与不同的同位素，通过改变外部磁场的ESR照射N-14和N-15核之间的场循环OMRI。OMRI同时获得了两个单独的化学过程的双重图像。氧化和还原在纳米尺度上的速率依赖性的方式进行监测，通过标记膜渗透性和非渗透性硝酰基自由基与N-14和N-15核。含有抗坏血酸封装的脂质体与膜渗透性自由基，但不是膜不渗透的幻影对象显示的OMRI图像强度的时间依赖性降低。采用OMRI评价小鼠体内的药代动力学。这种具有双探针的OMRI技术应该提供纳米尺度分子成像和基因修饰动物中独立过程的同时评估的显著适用性。因此，它可能成为阐明疾病机制和监测药物治疗的有力工具。
MRI has provided significant clinical utility in the diagnosis of diseases and will become a powerful tool to assess phenotypic changes in genetically engineered animals. Overhauser enhanced MRI (OMRI), which is a double resonance technique, creates images of free radical distributions in small animals by enhancing the water proton signal intensity by means of the Overhauser effect. Several studies have demonstrated noninvasive assessment of reactive oxygen species generation in small animals by using low frequency electron spin resonance (ESR) spectroscopy/imaging and nitroxyl radicals. In vivo ESR signal intensities of nitroxyl radicals decrease with time after injection; and the decreases are enhanced by reactive oxygen species, generated in oxidative disease models in a site-specific manner. In this study, we show images of nitroxyl radicals with different isotopes by changing the external magnetic field for ESR irradiation between N-14 and N-15 nuclei in field-cycled OMRI. OMRI simultaneously obtained dual images of two individual chemical processes. Oxidation and reduction were monitored in a rate-dependent manner at nanometer scale by labeling membrane-permeable and -impermeable nitroxyl radicals with N-14 and N-15 nuclei. Phantom objects containing ascorbic acid-encapsulated liposomes with membrane-permeable radicals but not membrane-impermeable ones show a time-dependent decrease of the OMRI image intensity. The pharmacokinetics in mice was assessed with OMRI after radical administration. This OMRI technique with dual probes should offer significant applicability to nanometer scale molecular imaging and simultaneous assessment of independent processes in gene-modified animals. Thus, it may become a powerful tool to clarify mechanisms of disease and to monitor pharmaceutical therapy.