CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
Magn Reson Med. 2009 Nov;62(5):1300-4. doi: 10.1002/mrm.22049.
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 (13)C 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 (13)C 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.
羧肽酶 G2（CPG2）是一种细菌酶，目前被应用于多种靶向癌症化疗策略中，如基因导向酶前药治疗（GDEPT）。本研究采用动态核极化（DNP）和自然丰度（13）C 磁共振波谱（MRS）技术，观察到 CPG2 介导的新型高极化报告探针 3,5-二氟苯甲酰-L-谷氨酸（3,5-DFBGlu）向 3,5-二氟苯甲酸（3,5-DFBA）和 L-谷氨酸（L-Glu）的体外转化。用（13）C 对 3,5-DFBGlu 或相关底物中相关核进行同位素标记，将使信号与噪声的比值进一步增加 100 倍。我们讨论了将这些实验转化为体内 CPG2 活性代谢图像的可行性。
