Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature
Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature
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DOI：
10.1097/rli.0b013e318164b71d
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发表时间：
2008-05-01
影响因子：
6.7
通讯作者：
Brasch, Robert C.
中科院分区：
文献类型：
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作者：
Cyran, Clemens C.;Sennino, Barbara;Brasch, Robert C.
目的：探讨基于大分子造影剂(MMCM)的动态增强磁共振血管成像定量分析技术在寻找和测量二甲基亚砜(DMSO)对肿瘤血管影响的可行性。材料和方法：用白蛋白(Gd-DTPA)(27)-(生物素)(11)(分子质量约90 kDa)对大鼠乳腺癌移植瘤(MDA-MB-435)进行MMCM增强MRI动态成像。材料和方法：用生理盐水对照组(n=8)和DMSO处理组(n=7)建立大鼠乳腺癌移植瘤模型。3剂疗程。治疗后MRI检查后，用凝集素和固定剂对肿瘤进行灌注，然后用RecA-1和链霉亲和素染色进行定量荧光显微镜观察。肿瘤微血管渗透性(K-PS；Mu L/min 100 cm(3))和血浆体积分数(Fpv；%)的MRI定量估计是基于二室动力学模型。结果：从肿瘤K(PS)d0=19.3+/-8.8亩L/分·100 cm(3)到K(PS)d7=0 mU L/min·100 cm(3)，二甲基亚砜显著降低肿瘤血管内皮细胞通透性(P<；0.05)。生理盐水处理的肿瘤K-PS值无明显变化。MMCM上生物素标记的荧光标记链霉亲和素染色显示，DMSO治疗组白蛋白-Gd-(DTPA)(27)-(生物素)(11)渗出量显著低于对照组(57.7%+/-5.5%vs.34.2%+/-4.9%)。结论：动态MMCM增强MRI可以检测和测量DMSO治疗7天后肿瘤微血管渗漏的减少，并被同一肿瘤中渗漏的大分子物质的显微镜测量所证实。结果支持MMCM增强的MRI方法在癌症特征方面的稳健性，并为DMSO对癌症血管的体内效应提供了第一个证据。
Objectives: To evaluate the potential of quantitative assays of vascular characteristics based on dynamic contrast-enhanced magnetic resonance imaging (MRI) using a macromolecular contrast medium (MMCM) to search for and measure effects of dimethyl sulfoxide (DMSO) on cancer vasculature with microscopic correlations.Material and Methods: Saline-treated control (n = 8) and DMSO-treated (n = 7) human breast cancer xenografts (MDA-MB-435) in rats were imaged dynamicall y by MMCM-enhanced MRI using albumin-(Gd-DTPA)(27)-(biotin)(11) (molecular weight approximately 90 kDa), before and after a 1-week, 3-dose treatment course. After the posttreatment MRI examinations, tumors were perfused with lectin and fixative and subsequently stained with RECA-1 and streptavidin for quantitative fluorescent microscopy. Quantitative MRI estimates of cancer microvessel permeability (K-PS; mu L/min.100 cm(3)) and fractional plasma volume (fPV; %) were based on a 2-compartment kinetic model. Fluorescent microscopy yielded estimates of MMCM extravasation and vascular density that were compared to the MRI results.Results: DMSO decreased cancer vascular endothelial permeability significantly (P < 0.05) from tumor K(PS)day0 = 19.3 +/- 8.8 mu L/min.100 cm(3) to K(PS)day7 = 0 mu L/min.100 cm(3)). K-PS values in the saline-treated tumors did not change significantly. The amount of extravasated albumin-Gd-(DTPA)(27)-(biotin)(11), as assayed by a fluorescently labeled streptavidin stain that strongly binds to the biotin tag on the MMCM, was significantly (P < 0.05) lower in the DMSO-treated cancers than in the control cancers (57.7% +/- 5.5% vs. 34.2% +/- 4.9%). Tumor vascular richness as reflected by the MRI-assayed fPV and by the RECA-1 and lectin-stained microscopy did not change significantly with DMSO or saline treatment.Conclusion: Reductions in cancer microvascular leakiness induced by a 7-day course of DMSO could be detected and measured by dynamic MMCM-enhanced MRI and were confirmed by microscopic measurements of the leaked macromolecular agents in the same cancers. Results support the robustness of an MMCM-enhanced MRI approach to the characterization of cancers and providing first evidence for an in vivo effect of DMSO on cancer blood vessels.