Hyperpolarized 13C Magnetic Resonance Detection of Carboxypeptidase G2 Activity
Hyperpolarized 13C Magnetic Resonance Detection of Carboxypeptidase G2 Activity
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DOI：
10.1002/mrm.22049
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发表时间：
2009-11-01
影响因子：
3.3
通讯作者：
Eykyn, Thomas R.
中科院分区：
文献类型：
--
作者：
Jamin, Yann;Gabellieri, Cristina;Eykyn, Thomas R.
羧肽酶G2（CPG 2）是一种细菌酶，目前用于一系列靶向癌症化疗策略，如基因导向酶前药治疗（GDEPT）。采用动态核极化（DNP）和天然丰度碳13核磁共振波谱（MRS）技术，观察了新型超极化报告探针3，5-二氟苯甲酰基-L-谷氨酸（3，5-DFBGlu）在体外由CPG 2介导转化为3，5-二氟苯甲酸（3，5-DFBA）和L-谷氨酸（L-Glu）的过程。在3，5-DFBGlu或相关底物中用C-13同位素标记相关核将产生信噪比的进一步增加100倍。我们讨论了将这些实验转化为体内CPG 2活性代谢图像的可行性。Magn Reson Med 62：1300-1304，2009. (C)2009威利-利斯公司
Carboxypeptidase G2 (CPG2) is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). Employing dynamic nuclear polarization (DNP) and natural abundance C-13 magnetic resonance spectroscopy (MRS), we observed the CPG2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu) to 3,5-difluorobenzoic acid (3,5-DFBA) and L-glutamic acid (L-Glu) in vitro. Isotopic labeling of the relevant nuclei with C-13 in 3,5-DFBGlu or related substrates will yield a further factor of 100 increase in the signal-to-noise. We discuss the feasibility of translating these experiments to generate metabolic images of CPG2 activity in vivo. Magn Reson Med 62:1300-1304, 2009. (C) 2009 Wiley-Liss, Inc.