Towards hyperpolarized 13C-succinate imaging of brain cancer
Towards hyperpolarized 13C-succinate imaging of brain cancer
复制标题
DOI：
10.1016/j.jmr.2007.01.017
复制
发表时间：
2007-05-01
影响因子：
2.2
通讯作者：
Weitekamp, Daniel P.
中科院分区：
文献类型：
--
作者：
Bhattacharya, Pratip;Chekmenev, Eduard Y.;Weitekamp, Daniel P.
我们描述了一种新的富含C-13的前体分子，l-C-13乙酰二羧酸钠，在受控的实验条件下通过PASADENA（对氢和合成允许显著增强核对准）加氢后，成为超极化的13C琥珀酸钠。快速体内3D FIESTA磁共振成像显示，在颈动脉注射后，正常和肿瘤大鼠的头部和脑循环中出现超极化的c -13-琥珀酸盐。目前，体内超极化信号尚未定位于正常大脑或脑肿瘤。另一方面，在颈动脉内注射超极化C-13琥珀酸钠1小时或更长时间后，从患有9L脑瘤的大鼠身上采集的离体脑样本中，含有显著浓度的注射底物C-13琥珀酸钠，以及C-13马来酸盐和琥珀酸盐代谢产物l-C-13-谷氨酸盐、5-C-13-谷氨酸盐、l-C-13-谷氨酰胺和5-C-13-谷氨酰胺。C-13底物和产物低于正常脑离体样品的核磁共振检测极限，与完整的血脑屏障一致。这些离体结果表明，超极化C-13琥珀酸钠可能成为快速体内鉴定脑肿瘤的有用工具，为13C MR光谱空间图像提供新的生物标志物。(C) 2007爱思唯尔公司版权所有。
We describe a novel C-13 enriched precursor molecule, sodium l-C-13 acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized C-13-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized C-13 sodium succinate, contained significant concentrations of the injected substrate, C-13 sodium succinate, together with C-13 maleate and succinate metabolites l-C-13-glu- tamate, 5-C-13-glutamate, l-C-13-glutamine and 5-C-13-glutamine. The C-13 substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized C-13 sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. (C) 2007 Elsevier Inc. All rights reserved.