谷氨酰胺
胶质瘤
体内
IDH1
新陈代谢
癌症研究
生物
化学
生物化学
突变体
氨基酸
基因
生物技术
作者
Sriram Venneti,Mark P. Dunphy,Hui Zhang,Kenneth L. Pitter,C. Campos,Stephen M. Carlin,Serge K. Lyashchenko,C. Ploessl,Daniel Rohle,Antonio M. P. Omuro,Justin R. Cross,Cameron Walter Brennan,Wolfgang Weber,Eric C. Holland,Ingo K. Mellinghoff,Hank F. Kung,J J Lewis,Craig B. Thompson
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2014-11-01
卷期号:16 (suppl 5): v216-v216
标识
DOI:10.1093/neuonc/nou278.14
摘要
Glutamine is the most abundant plasma amino acid and many cancers show altered glutamine metabolism. We evaluated glutamine uptake and metabolism in gliomas using PET imaging and biochemical approaches. We demonstrate that glutamine is a key TCA cycle anaplerotic substrate and is metabolized to generate 2-HG in IDH1-mutant gliomas. PET imaging with18F-labeled glutamine (18F-FGln) showed high uptake in gliomas in vivo but low background uptake in the surrounding brain in RCAS-PDGF/PTEN null and IDH1-mutant glioma animal models, facilitating clear tumor delineation in contrast to that seen with 18F-FDG. We did not observe 18F-FGln uptake in animals with neuroinflammation or animals with a disrupted BBB. Further, 18F-FGln uptake was specifically reduced on chemo/radiation therapy. Finally, 18F-FGln showed high avidity in human glioma with low uptake in the surrounding brain. These data suggest that 18F-FGln is specifically taken up by gliomas, can be used to assess the metabolic state of gliomas in vivo and may serve as a valuable tool in the clinical management of gliomas.
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