Towards hyperpolarized ¹³C-succinate imaging of brain cancer

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• 作者：Pratip Bhattacharya ; Eduard Y. Chekmenev ; William H. Perman ; Kent C. Harris ; Alex ; er P. Lin ; Valerie A. Norton ; Chou T. Tan ; Brian D. Ross ; Daniel P. Weitekamp
• 关键词：PASADENA ; Hyperpolarization ; ¹³C ; Succinate ; Acetylenedicarboxylate ; 9L tumor ; Glutamine ; In vivo imaging ; Ex vivo spectroscopy
• 刊名：Journal of Magnetic Resonance
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：186
• 期：1
• 页码：150-155
• 全文大小：416 K

文摘

We describe a novel ¹³C enriched precursor molecule, sodium 1-¹³C 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 ¹³C-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 ¹³C sodium succinate, contained significant concentrations of the injected substrate, ¹³C sodium succinate, together with ¹³C maleate and succinate metabolites 1-¹³C-glutamate, 5-¹³C-glutamate, 1-¹³C-glutamine and 5-¹³C-glutamine. The ¹³C 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 ¹³C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in ¹³C MR spectral-spatial images.