RT Journal Article
SR Electronic
T1 <strong>L-[5-11C]glutamine PET monitors dynamic responses of glutaminolysis to interventions targeting glutaminase 1 in non-alcoholic steatohepatitis </strong>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 241367
OP 241367
VO 65
IS supplement 2
A1 Xie, Lin
A1 Zhang, Yiding
A1 Fujinaga, Masayuki
A1 Kurihara, Yusuke
A1 Ogawa, Masanao
A1 Kumata, Katsushi
A1 Wakana, Mori
A1 Kokufuta, Tomomi
A1 Nengaki, Nobuki
A1 Wakizaka, Hidekatsu
A1 Luo, Rui
A1 Zhang, Ming-Rong
YR 2024
UL http://jnm.snmjournals.org/content/65/supplement_2/241367.abstract
AB 241367 Introduction: Interventions targeting glutaminolysis has been proposed as a potential treatment strategy for non-alcoholic steatohepatitis (NASH).1,2 However, effective methods for assessing dynamic metabolic responses during interventions targeting glutaminolysis have not yet emerged. In this study, we developed a positron emission tomography (PET) imaging platform using L-[5-11C]glutamine ([11C]Gln) and evaluated its efficacy in NASH mice, as well as during metabolic therapy with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) (Fig. 1).Methods: Utilising [11C]Gln PET, we tracked the dynamic response of glutaminolysis under normal physiological conditions, in murine models of NASH induced by methionine and choline deficient (MCD) diet,3 and following therapeutic interventions with BPTES, a glutaminase 1 (GLS1) inhibitor that intervenes in the first and rate-limiting step of glutaminolysis.1,2 Histopathological and genetic analyses were performed to evaluate and quantify hepatic GLS1 levels and liver pathologies.Results: 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 NASH mice, whereas systemic therapeutic interventions with BPTES reduced the hepatic avidity of [11C]Gln in MCD diet-fed mice(Fig. 1A-B). This reduction in [11C]Gln uptake correlated with a decrease in the GLS1 burden and improvements in liver damage, suggesting the efficacy of BPTES in mitigating NASH-related metabolic abnormalities(Fig. 1C).Conclusions: 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. References• Johmura Y, Yamanaka T, Omori S, et al. Science 2021;371:265-270.• Simon J, Nuñez-García M, Fernández-Tussy P, et al. T Cell Metab 2020;31:605-622.e610.• Xie L, Yui J, Hatori A, et al. J Hepatol 2012;57:1076-1082.