Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Unitat de Biociències, Edifici C, Cerdanyola del Vallès, Spain.
NMR Biomed. 2013 Feb;26(2):173-84. doi: 10.1002/nbm.2832. Epub 2012 Jul 20.
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 µmol/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 T(1) 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 blood-brain 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.
二甲基亚砜（DMSO）常用于高级别神经胶质瘤动物模型的临床前研究中，作为化疗药物的溶剂。在一项关于灌胃后 DMSO 耐受性的初步研究中，三只 C57BL/6 对照小鼠的脑内通过单体素 MRS 检测到强烈的 DMSO 信号。这促使我们通过单体素 MRS 研究 DMSO 在正常脑实质（n=3 只对照小鼠）和 12 个 GL261 胶质母细胞瘤（GBM）中的积累和洗脱动力学（n=3 个单体素 MRS 和 n=9 个 MRSI）。DMSO 在每种组织类型中的积累方式不同，在肿瘤中达到最高浓度：6.18±0.85µmol/g 水，比对照小鼠脑高 1.5 倍（p<0.05）。与 GBM 组织相比，正常脑实质中的洗脱速度更快：半衰期分别为 2.06±0.58 和 4.57±1.15h。时间过程中 DMSO 变化的 MRSI 图谱显示，GL261 肿瘤中存在明显的空间积累差异热点。对四只携带少突胶质细胞瘤（OD）的小鼠进行的额外 MRSI 研究显示出与 GBM 肿瘤相似的结果。对照小鼠脑和 OD 小鼠在钆后缺乏 T(1)对比增强（钆喷替酸二葡甲胺，Gd-DTPA）表明，DMSO 完全能够穿过正常脑实质和低级别肿瘤的完整血脑屏障。我们的研究结果表明，DMSO 作为脑肿瘤检测的对比剂具有潜在作用，即使在那些对标准钆增强 MRI 不可见的肿瘤中也是如此，并且可能用于监测与进展或治疗反应相关的异质性。
