l-5-11CGlutamine PET imaging noninvasively tracks dynamic responses of glutaminolysis in non-alcoholic steatohepatitis.
10.1016/j.apsb.2024.07.023
- Author:
Yiding ZHANG
1
;
Lin XIE
1
;
Masayuki FUJINAGA
1
;
Yusuke KURIHARA
1
;
Masanao OGAWA
1
;
Katsushi KUMATA
1
;
Wakana MORI
1
;
Tomomi KOKUFUTA
1
;
Nobuki NENGAKI
1
;
Hidekatsu WAKIZAKA
1
;
Rui LUO
1
;
Feng WANG
2
;
Kuan HU
3
;
Ming-Rong ZHANG
1
Author Information
1. Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
2. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
3. 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.
- Publication Type:Journal Article
- Keywords:
BPTES therapy;
Glutaminase 1;
Glutaminolysis;
Metabolic intervention;
Non-alcoholic steatohepatitis;
Positron emission tomography;
l-[5-11C]Glutamine
- From:
Acta Pharmaceutica Sinica B
2025;15(2):681-691
- CountryChina
- Language:English
-
Abstract:
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-[5-11C]glutamine ([11C]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 [11C]Gln effectively delineated the pharmacokinetics of l-glutamine, capturing its temporal-spatial pattern of action within the body. Furthermore, [11C]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 [11C]Gln in MCD-fed mice. This reduction in [11C]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 [11C]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.
