Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research, Sutton, Surrey SM2 5PT, England.
Radiology. 2010 Jan;254(1):110-8. doi: 10.1148/radiol.2541090395.
To investigate relationships between magnetic resonance (MR) imaging measurements of R2* and carbogen-induced DeltaR2* in vivo with subsequent histologic assessment of grade, hypoxia, fibrosis, and necrosis in a chemically induced rat mammary tumor model.
All experiments were performed in accordance with the local ethics review panel, the UK Home Office Animals Scientific Procedures Act of 1986, and the UK Co-ordinating Committee on Cancer Research guidelines. Of 30 rats injected with N-methyl-N-nitrosourea, 17 developed mammary tumors. Prior to MR imaging, rats were administered pimonidazole. Tumor R2* was then quantified while the host first breathed air and then carbogen (95% O(2), 5% CO(2); n = 16). Tumor sections were subsequently stained for pimonidazole, sirius red, cytokeratin 14, and hematoxylin-eosin for quantitative assessment of hypoxia, fibrosis, malignancy, and necrosis, respectively, and graded according to the Scarff-Bloom-Richardson scale. Linear regression analysis was used to identify any correlates of the MR imaging data with histologic data.
Tumors exhibited wide heterogeneity in the magnitude of carbogen-induced reduction in R2*, an emerging imaging biomarker of fractional blood volume. Significant correlations were found between pimonidazole adduct formation and both baseline tumor R2* (r = -0.54, P = .03) and carbogen-induced DeltaR2* (r = 0.56, P = .02), demonstrating that tumors with a larger fractional blood volume were less hypoxic. There was also a significant correlation between pimonidazole and sirius red staining (r = 0.76, P < .01), indicating that more fibrotic tumors were also more hypoxic. There were no correlations of R2* with grade.
In this model of breast cancer, baseline tumor R2* and carbogen-induced DeltaR2* are predictive imaging biomarkers for hypoxia and primarily determined by blood volume.
研究体内磁共振（MR）成像 R2测量值与碳氧诱导 DeltaR2之间的关系，并通过化学诱导的大鼠乳腺肿瘤模型对分级、缺氧、纤维化和坏死进行后续组织学评估。
所有实验均符合当地伦理审查小组、英国 1986 年动物科学程序法案和英国癌症研究协调委员会指南的规定。在注射 N-甲基-N-亚硝脲的 30 只大鼠中，有 17 只发展为乳腺肿瘤。在 MR 成像之前，大鼠给予了 pimonidazole。然后，在宿主首先呼吸空气然后呼吸碳氧（95% O2，5% CO2；n = 16）的情况下，对肿瘤的 R2*进行定量。随后，对肿瘤切片进行 pimonidazole、天狼星红、细胞角蛋白 14 和苏木精-伊红染色，分别定量评估缺氧、纤维化、恶性和坏死，并根据 Scarff-Bloom-Richardson 分级进行分级。线性回归分析用于确定 MR 成像数据与组织学数据之间的任何相关性。
肿瘤在碳氧诱导的 R2降低幅度上表现出广泛的异质性，这是一个新兴的血容量分数成像生物标志物。pimonidazole 加合物形成与基线肿瘤 R2（r = -0.54，P =.03）和碳氧诱导的 DeltaR2*（r = 0.56，P =.02）之间存在显著相关性，表明血容量较大的肿瘤缺氧程度较低。pimonidazole 与天狼星红染色之间也存在显著相关性（r = 0.76，P <.01），表明更纤维化的肿瘤也更缺氧。R2*与分级之间无相关性。
在这种乳腺癌模型中，基线肿瘤 R2和碳氧诱导的 DeltaR2是缺氧的预测性成像生物标志物，主要由血容量决定。
