Department of Radiology and Biomedical Imaging, Mission Bay Campus, University of California, 1700 4th Street, Byers Hall, 94158, San Francisco, CA, United States.
Department of Chemistry and Biotechnology, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2020 Apr 10;10(1):6244. doi: 10.1038/s41598-020-63160-y.
Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-C]glycine and acquiring dynamic C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-C]glycine and its product [1-C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.
谷胱甘肽（GSH）在癌症中经常上调，在癌症中它有助于减轻氧化应激。γ-谷氨酰转移酶（GGT）是 GSH 动态平衡的关键酶，与正常大脑相比，其在肿瘤中的表达升高，包括原发性神经胶质瘤。因此，GGT 是检测神经胶质瘤的有吸引力的成像靶点。我们的研究目的是评估超极化（HP）γ-谷氨酰-[1-C]甘氨酸在神经胶质瘤无创成像中的价值。我们研究了荷原位 U87 神经胶质瘤的裸鼠和健康对照。通过注射 HP γ-谷氨酰-[1-C]甘氨酸并在临床前 3T MR 扫描仪上采集动态 C 数据来进行成像。评估了γ-谷氨酰-[1-C]甘氨酸及其产物[1-C]甘氨酸的信号与噪声（SNR）比。对照和荷瘤大鼠的比较显示，γ-谷氨酰-[1-C]甘氨酸的 SNR 没有差异，表明其向肿瘤和正常大脑的输送相似。相比之下，与对照组相比，荷瘤大鼠的[1-C]甘氨酸 SNR 显著更高，并且在肿瘤区域与正常脑相比更高。重要的是，与正常脑相比，肿瘤组织中更高的[1-C]甘氨酸与肿瘤组织中更高的 GGT 表达和更高的 GSH 水平相关。总之，这项研究首次证明了使用 HP γ-谷氨酰-[1-C]甘氨酸监测大脑中 GGT 表达并因此检测神经胶质瘤的可行性。
