l-[5-^(11)C]Glutamine PET imaging noninvasively tracks dynamic responses of glutaminolysis in non-alcoholic steatohepatitis Author links open overlay panel  

作　　者：Yiding Zhang Lin Xie Masayuki Fujinaga Yusuke Kurihara Masanao Ogawa Katsushi Kumata Wakana Mori Tomomi Kokufuta Nobuki Nengaki Hidekatsu Wakizaka Rui Luo Feng Wang Kuan Hu Ming-Rong Zhang 

机构地区：[1]Department of Advanced Nuclear Medicine Sciences,Institute for Quantum Medical Science,National Institutes for Quantum Science and Technology,Chiba 263-8555,Japan [2]SHI Accelerator Service,Ltd,Tokyo 141-0031,Japan [3]Department of Nuclear Medicine,Nanjing First Hospital,Nanjing Medical University,Nanjing 210006,China [4]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期681-691,共11页药学学报(英文版)

基　　金：supported in part by the Moonshot Research and Development Program(Grant No.21zf0127003h001,Japan);JSPS A3 Foresight Program(Grant No.JPJSA3F20230001,Japan);JSPS KAKENHI(Grants No.23H02867,23H05487,and 21K07659,Japan).

摘　　要：Inhibiting glutamine metabolism has been proposed as a potential treatment strategy for improving non-alcoholic steatohepatitis(NASH).However,effective methods for assessing dynamic metabolic responses during interventions targeting glutaminolysis have not yet emerged.Here,we developed a positron emission tomography(PET)imaging platform using l-[5-^(11)C]glutamine([^(11)C]Gln)and evaluated its efficacy in NASH mice undergoing metabolic therapy with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide(BPTES),a glutaminase 1(GLS1)inhibitor that intervenes in the first and rate-limiting step of glutaminolysis.PET imaging with[^(11)C]Gln effectively delineated the pharmacokinetics of l-glutamine,capturing its temporal-spatial pattern of action within the body.Furthermore,[^(11)C]Gln PET imaging revealed a significant increase in hepatic uptake in methionine and choline deficient(MCD)-fed NASH mice,whereas systemic therapeutic interventions with BPTES reduced the hepatic avidity of[^(11)C]Gln in MCD-fed mice.This reduction in[^(11)C]Gln uptake correlated with a decrease in GLS1 burden and improvements in liver damage,indicating the efficacy of BPTES in mitigating NASH-related metabolic abnormalities.These results suggest that[^(11)C]Gln PET imaging can serve as a noninvasive diagnostic platform for whole-body,real-time tracking of responses of glutaminolysis to GLS1 manipulation in NASH,and it may be a valuable tool for the clinical management of patients with NASH undergoing glutaminolysis-based metabolic therapy.

关 键 词：l-[5-^(11)C]Glutamine Positron emission tomography Non-alcoholic steatohepatitis GLUTAMINOLYSIS Glutaminase 1 Metabolic intervention BPTES therapy 

分 类 号：R575.5[医药卫生—消化系统]