High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents
High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents
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DOI：
10.1158/1078-0432.ccr-05-2747
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发表时间：
2006-04-15
影响因子：
11.5
通讯作者：
Krishna, MC
中科院分区：
文献类型：
--
作者：
Matsumoto, K;Hyodo, F;Krishna, MC
目的：有相当多的研究针对识别和开发用于医学成像的功能性造影剂，其将组织生化/分子信息与解剖结构结合起来。氮氧自由基被确定为在体内的辐射保护。由于具有顺磁性，它们可以在磁共振成像（MRI）和电子顺磁共振成像（EPRI）中提供图像对比度。本研究旨在确定氮氧化物radioprotectors作为功能性图像contradengers.Experimental设计的功效：氮氧化物radioprotectors，作为造影剂，进行了测试，EPRI和MRI提供组织的氧化还原状态信息非侵入性。结果如下：体模研究表明，氮氧自由基，3-氨基甲酰基-PROXYL（3CP），经历时间依赖性还原为相应的抗磁性羟胺只有在还原剂的存在下。EPRI和MRI测定的3CP降低率一致，提示MRI监测组织中氮氧自由基水平的可行性。通过EPRI和MRI检查3CP水平，以确定同时植入C3 H小鼠后腿的肌肉和肿瘤（鳞状细胞癌）之间的减少差异。体内实验表明，3CP提供的T1依赖性图像强度增强以时间依赖性方式降低。发现3CP的减少是对比度损失的主要机制。肿瘤区域表现出更快的衰减率的氮氧化物相比，肌肉（0.097分钟（-1）与0.067分钟（-1），分别）。结论：这项研究表明，MRI可以成功地用于共同注册组织氧化还原状态沿着与解剖图像，从而提供潜在的有价值的生化信息，从感兴趣的区域。
Purpose: There is considerable research directed toward the identification and development of functional contrast agents for medical imaging that superimpose tissue biochemical/molecular information with anatomical structures. Nitroxide radicals were identified as in vivo radioprotectors. Being paramagnetic, they can provide image contrast in magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). The present study sought to determine the efficacy of nitroxide radioprotectors as functional image contrast agents.Experimental Design: Nitroxide radioprotectors, which act as contrast agents, were tested by EPRI and MRI to provide tissue redox status information noninvasively. Results: Phantom studies showed that the nitroxide, 3-carbamoyl-PROXYL (3CP), undergoes time-dependent reduction to the corresponding diamagnetic hydroxylamine only in the presence of reducing agents. The reduction rates of 3CP obtained by EPRI and MRI were in agreement suggesting the feasibility of using MRI to monitor nitroxide levels in tissues. The levels of 3CP were examined by EPRI and MRI for differences in reduction between muscle and tumor (squamous cell carcinoma) implanted in the hind leg of C3H mice simultaneously. In vivo experiments showed a T1-dependent image intensity enhancement afforded by 3CP which decreased in a time-dependent manner. Reduction of 3CP was found to be the dominant mechanism of contrast loss. The tumor regions exhibited a faster decay rate of the nitroxide compared to muscle (0.097 min(-1) versus 0.067 min(-1), respectively).Conclusions: This study shows that MRI can be successfully used to co-register tissue redox status along with anatomic images, thus providing potentially valuable biochemical information from the region of interest.