In vivo measurement of regional oxygenation and Imaging of redox status in RIF-1 murine tumor: Effect of carbogen-breathing

In vivo measurement of regional oxygenation and Imaging of redox status in RIF-1 murine tumor: Effect of carbogen-breathing
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DOI:
10.1002/mrm.10254
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发表时间:
2002-10-01
影响因子:
3.3
通讯作者:
Kuppusamy, P
Kuppusamy, P
中科院分区:
医学3区
文献类型:
--
作者:
Ilangovan, G;Li, HQ;Kuppusamy, P

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本研究的目的是在小鼠肿瘤模型中,使用体内电子顺磁共振(EPR)光谱和成像技术,在高氧治疗(如碳源呼吸)期间无创监测肿瘤氧合和氧化还原状态。在C3 H小鼠上后肢植入的RIF-1肿瘤中,使用植入的酞菁锂(LiPc)微晶作为血氧测定探针和3-氨基甲酰基乙酰基(3-CP)作为氧化还原探针进行研究。重复测量同一肿瘤的pO(2)作为肿瘤生长(8-24 mm大小)的函数,表明肿瘤缺氧,肿瘤pO(2)值随肿瘤生长而降低。碳源呼吸主要表现为肿瘤氧合的增加,尽管肿瘤之间的变化幅度存在相当大的差异。3-CP的药代动力学研究显示,在碳源呼吸小鼠中总体肿瘤缩小状态显著降低。获得了肿瘤体积上的空间分辨(成像)药代动力学数据,以可视化肿瘤内氧化还原状态的分布。在空气呼吸小鼠的肿瘤的氧化还原图像显示出显着的异质性的大小和空间分布的还原当量。在碳源呼吸的组织还原状态大大降低,伴随着减少的氧化还原状态的分布的异质性。结果表明:1)碳源呼吸大大增强了RIF-1肿瘤的组织氧合,并显着降低了RIF-1肿瘤的氧化还原状态,2)碳源呼吸期间肿瘤体积内氧化还原状态的大小和分布的变化与组织氧合的增加相关。(C)2002 Wiley-Liss,Inc.
The purpose of this study was to noninvasively monitor tumor oxygenation and redox status during hyperoxygenation treatment, such as carbogen-breathing, in a murine tumor model using in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques. The study was performed using implanted lithium phthalocyanine (LiPc) microcrystals as the oximetry probe and 3-carbamoylproxyl (3-CP) as the redox probe in RIF-1 tumors implanted in the upper hind leg of C3H mice. Repetitive measurements of pO(2) from the same tumors as a function of tumor growth (8-24 mm in size) showed that the tumors were hypoxic and that the tumor pO(2) values were decreasing with tumor growth. Carbogen-breathing mostly showed an increase in the tumor oxygenation, although there were considerable variations in the magnitude of change among the tumors. The pharmacokinetic studies with 3-CP showed a significant decrease in the overall tumor reduction status in the carbogen-breathing mice. Spatially resolved (imaging) pharmacokinetic data over the tumor volume were obtained to visualize the distribution of the redox status within the tumor. The redox images of the tumor in the air-breathing mice showed significant heterogeneity in the magnitude and spatial distribution of reducing equivalents. On carbogen-breathing the tissue reduction status decreased considerably, with a concomitant decrease in the heterogeneity of distribution of the redox status. The results suggest that 1) carbogen-breathing considerably enhances tissue oxygenation and significantly decreases the redox status in RIF-1 tumor, and 2) changes in the magnitude and distribution of the redox status within the tumor volume during carbogen-breathing are correlated with the increased tissue oxygenation. (C) 2002 Wiley-Liss, Inc.