A redox-activated MRI contrast agent that switches between paramagnetic and diamagnetic states.
A redox-activated MRI contrast agent that switches between paramagnetic and diamagnetic states.
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DOI：
10.1002/anie.201306394
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发表时间：
2013-12-23
影响因子：
16.6
通讯作者：
Morrow, Janet R.
中科院分区：
文献类型：
--
作者：
Tsitovich, Pavel B.;Spernyak, Joseph A.;Morrow, Janet R.
用于生产响应性或“智能”显像剂的分子开关的设计是一个重大挑战。特别令人感兴趣的是对生物氧化还原环境做出反应的试剂，以绘制涉及氧化还原失衡的疾病状态。 [1]氧化还原失衡可能通过多种方式引发，包括实体瘤中氧压极低或缺氧。 [2]重要的是，绘制肿瘤组织的氧水平和相应氧化还原状态的探针的开发可能会指导肿瘤选择性药物的开发。[3]正如最近综述的那样，有几种类型的成像剂可以报告生物氧化还原状态。[1]放射诊断探针包括 19F-氟米索硝唑和 64Cu 复合物，用于通过正电子发射断层扫描 (PET) 对缺氧肿瘤组织进行成像。氮氧化物自旋标记用于通过 ESR 绘制氧水平图 一种类型的磁共振成像 (MRI) 方法基于氟化烃中 19F 信号的氧依赖性。或者，血氧水平依赖性 MRI (BOLD-MRI) 可以追踪顺磁性脱氧血红蛋白浓度的变化。具有氧化还原响应的金属基 MRI 造影剂包括具有基于配体的氧化还原开关的 Ln (III) 造影剂。 [4]一种优雅的方法是使用造影剂与 Mn (II)/Mn (III) 对进行基于金属的氧化还原，从而改变 T1 弛豫率。 [5]后一种方法的挑战之一是磁特性的相对较小的差异会调节 MRI 对比度。 Co (II)/Co (III) 是一种金属氧化还原电对，它的磁性会发生很大的变化，并且在生物相关范围内具有出色的可调性。据我们所知，在这里我们提出了氧化还原活性 MRI 造影剂的第一个例子，它可以在顺磁和抗磁状态之间切换，分别产生 MRI 活性和 MRI 无声复合物。
The design of molecular switches for the production of responsive or “smart” imaging agents is a major challenge. Of particular interest are agents that respond to biological redox environment to map those disease states that involve redox imbalances.[1] Redox imbalances may be triggered in many ways, including very low oxygen pressure or hypoxia in the case of solid tumors.[2] Importantly, the development of probes to map oxygen levels and corresponding redox status of tumor tissue may guide the development of tumor-selective drugs.[3]There are several types of imaging agents that report on biological redox status as recently reviewed.[1] Radiodiagnostic probes include 19F-fluoromisonidazole and 64Cu complexes for imaging hypoxic tumor tissue by positron emission tomography (PET). Nitroxide spin labels are used to map oxygen levels by ESR One type of magnetic resonance imaging (MRI) method is based on the oxygen dependence of the 19F signal in fluorinated hydrocarbons. Alternatively, blood-oxygenation level-dependent MRI (BOLD-MRI) tracks changes in paramagnetic deoxyhemoglobin concentration. Metal-based MRI contrast agents that are redox-responsive include Ln (III) contrast agents that feature ligand-based redox switches.[4] An elegant approach employs contrast agents that undergo metal-based redox with the Mn (II)/Mn (III) couple to give a change in T1 relaxivity.[5] One of the challenges with the latter approach is that relatively small differences in the magnetic properties modulate MRI contrast. A metal redox couple that undergoes large changes in magnetic properties and is eminently tunable in the biologically relevant range is Co (II)/Co (III). Here we present, to the best of our knowledge, the first example of a redox active MRI contrast agent that switches between paramagnetic and diamagnetic states to produce MRI active and MRI silent complexes, respectively.
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影响因子：
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影响因子：
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通讯作者：
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