Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors
Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors
复制标题
DOI：
10.1002/nbm.2832
复制
发表时间：
2013-02-01
影响因子：
2.9
通讯作者：
Arus, C.
中科院分区：
文献类型：
--
作者：
Delgado-Goni, T.;Martin-Sitjar, J.;Arus, C.
二甲基亚砜(DMSO)通常用于高级别胶质瘤动物模型的临床前研究，作为化疗药物的溶剂。在一项灌胃给药后DMSO耐受性的初步研究中，用单体素MRS在三只C57BL/6对照组小鼠的大脑中检测到强烈的DMSO信号。这使得我们通过单体素MRS研究了DMSO在正常脑实质(n=3只对照小鼠)中的积聚和洗出动力学，并通过单体素MRS(n=3)和MRSI(n=9)研究了12例GL261胶质母细胞瘤(GBM)中DMSO的积聚和洗出动力学。DMSO在不同组织类型中的积聚不同，在肿瘤中达到最高浓度：6.18+/-0.85mU/g水，是对照组小鼠脑内的1.5倍(p<；0.05)。与基底膜组织相比，正常脑组织的半衰期较快：半衰期分别为2.06±0.58和4.57±1.15小时。时程DMSO变化的MRSI图显示GL261肿瘤有明显的差异性空间聚集热点。另外，对四只携带少突胶质细胞瘤(OD)的小鼠进行的磁共振成像研究显示，结果与在GBM肿瘤中相似。Gd-DTPA在对照组和ODs组小鼠脑内缺乏T1对比剂增强，提示DMSO在正常脑实质和低级别肿瘤中完全能够穿过完整的血脑屏障。我们的结果表明，DMSO作为脑肿瘤检测的造影剂具有潜在的作用，甚至在那些标准的Gd增强MRI看不见的肿瘤中也是如此，并可能用于监测与进展或治疗反应相关的异质性。版权所有(C)2012 John Wiley&Sons，Ltd.
Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n = 3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n = 3) and MRSI (n = 9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 +/- 0.85 mu mol/g water, 1.5-fold higher than in control mouse brain (p < 0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 +/- 0.58 and 4.57 +/- 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T1 contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact bloodbrain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors invisible to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright (c) 2012 John Wiley & Sons, Ltd.