In vivo electron paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model.
In vivo electron paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model.
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发表时间：
1998-04
期刊：
影响因子：
11.2
通讯作者：
P. Kuppusamy;M. Afeworki;R. A. Shankar;D. Coffin;M. Krishna;S. Hahn;James B. Mitchell;J. Zweier
中科院分区：
文献类型：
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作者：
P. Kuppusamy;M. Afeworki;R. A. Shankar;D. Coffin;M. Krishna;S. Hahn;James B. Mitchell;J. Zweier
氮氧化物是氧化还原敏感的探针，在非侵入性描述组织异质性方面很有用，特别是在代谢活性和组织氧合方面。最近的研究表明，与肿瘤组织相比，氮氧化物在体外和体内都是放射防护剂，对正常组织具有选择性保护作用。据推测，与正常组织相比，肿瘤组织中氮氧化物的生物还原是对正常组织进行选择性放射防护的基础。本研究的目的是研究氮氧化物在肿瘤和正常组织中的分布和寿命。在小鼠的大腿上植入肿瘤细胞(RIF-1)，让肿瘤生长到直径约10-15毫米。静脉注射后。注射氮氧化物，体内电子顺磁共振波谱和肿瘤成像使用专门建造的桥环表面谐振器进行。观察了氮氧化物在肿瘤组织中的药代动力学和空间分布，并与正常组织进行了比较。三维空间图像显示氮氧化物的分布和还原速率具有明显的异质性。肿瘤组织中氮氧还原率明显高于正常组织。使用自旋标记血氧仪的测量表明，正常组织(肌肉)和肿瘤组织之间的氧合水平存在显著差异。肿瘤组织的平均PO2水平被发现比相应体积的正常组织低3倍。与正常组织相比，肿瘤组织中的PO2水平较低，这可能是这些组织中氮氧化物减少更快的原因。这项研究表明，电子顺磁共振成像可以进行非侵入性的解剖成像和功能成像，并提供关于肿瘤和正常组织细胞代谢的在体生理信息。
Nitroxides are redox-sensitive probes, which are useful in noninvasively delineating tissue heterogeneity especially with respect to metabolic activity and tissue oxygenation. Recent studies have shown that nitroxides are in vitro and in vivo radioprotectors and selectively protect normal tissue compared to tumor tissue. It has been postulated that the basis for selective radioprotection of normal tissues is greater bioreduction of nitroxides in tumor tissue compared to normal tissue. The aim of the present study was to investigate the distribution and lifetime of nitroxides in tumor and normal tissues. Mice were implanted with tumor cells (RIF-1) in the thigh, and the tumor was allowed to grow to about 10-15 mm in diameter. After i.v. infusion of nitroxides, in vivo electron paramagnetic resonance spectroscopy and imaging of the tumor were performed using a specially built bridged-loop surface resonator. The pharmacokinetic and spatial distribution of the nitroxides in tumor tissue were followed and compared with those in normal tissue. Three-dimensional spatial images showed significant heterogeneity in the nitroxide distribution as well as reduction rates. The nitroxide reduction rates were significantly higher in tumors than in the normal tissue. Measurements using spin label oximetry showed a substantial difference in the level of oxygenation between normal tissue (muscle) and tumor tissue. Average pO2 levels in tumor tissue were found to be 3-fold lower than in a corresponding volume of normal tissue. The lower pO2 levels in tumor compared to normal tissue may explain the more rapid reduction of nitroxides in these tissues. This study demonstrates that electron paramagnetic resonance imaging can perform noninvasive anatomical as well as functional imaging and provide in vivo physiological information regarding cellular metabolism in tumor and normal tissues.