[18F]FDG-PET provides insights into the liver-brain axis and confirms SUVgluc as a surrogate for MRGlu in a mouse model of liver fibrosis

IF 3 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-11-01 Epub Date: 2025-09-04 DOI:10.1016/j.nucmedbio.2025.109095

Thomas Wanek , Mari Teuter , Asha Balakrishnan , Tobias L. Ross , Frank M. Bengel , Michael Ott , Marion Bankstahl , Jens P. Bankstahl

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Abstract

Purpose

The liver-brain axis regulates metabolic homeostasis, with glucose metabolism playing a key role. Liver dysfunction, such as fibrosis, may impact brain metabolism and consequently, brain function. Positron emission tomography (PET) imaging provides a non-invasive approach to study glucose metabolism in both organs. A recent longitudinal PET/CT study utilizing 2-deoxy-2-[¹⁸F]-fluoro-d-glucose ([¹⁸F]FDG) amongst other radiotracers revealed significant metabolic changes in the liver in a mouse model of liver fibrosis. Here, we retrospectively analyzed those data to quantify potential associated changes in brain glucose metabolism.

Procedures

Eleven male C57BL/6N mice underwent repeated PET imaging with [¹⁸F]FDG at baseline, pre-fibrosis, fibrosis, and remission stages. Cerebral glucose metabolism was assessed using standardized uptake value (SUV), blood glucose-corrected SUV (SUV_gluc), and kinetic modeling (Patlak and two-tissue compartment models) for calculation of the glucose metabolic rate (MR_Glu).

Results

Both SUV_gluc and MR_Glu significantly decreased during pre-fibrosis and fibrosis on whole brain level and recovered at remission. SUV_gluc statistical parametric mapping identified multiple brain areas with reduced glucose metabolism, which was confirmed by regional analysis showing progressive reduction in SUV_gluc. Correlation analyses confirmed SUV_gluc as a reliable surrogate for MR_Glu, unlike uncorrected SUV. Liver [¹⁸F]FDG uptake increased during fibrosis and normalized at remission, mirroring changes in blood glucose concentrations.

Conclusions

[¹⁸F]FDG PET imaging revealed that liver fibrosis alters glucose metabolism in both liver and brain, emphasizing the potential of molecular imaging for future assessment of metabolic interaction between liver and brain. [¹⁸F]FDG uptake in terms of SUV_gluc strongly correlated with MR_Glu from kinetic modeling, supporting its utility as a valid surrogate parameter to quantify cerebral glucose metabolism in mice.

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[18F]FDG-PET提供了对肝-脑轴的深入研究，并证实了SUVgluc在小鼠肝纤维化模型中可以替代MRGlu

目的肝脑轴调节代谢稳态，其中葡萄糖代谢起关键作用。肝功能障碍，如肝纤维化，可能影响脑代谢，从而影响脑功能。正电子发射断层扫描（PET）成像提供了一种非侵入性的方法来研究两个器官的葡萄糖代谢。最近一项利用2-脱氧-2-[18F]-氟-d-葡萄糖（[18F]FDG）等放射性示踪剂的纵向PET/CT研究显示，在肝纤维化小鼠模型中肝脏发生了显著的代谢变化。在这里，我们回顾性地分析了这些数据，以量化脑葡萄糖代谢的潜在相关变化。11只雄性C57BL/6N小鼠在基线、纤维化前、纤维化和缓解期用[18F]FDG重复PET成像。采用标准化摄取值（SUV）、血糖校正SUV （SUVgluc）和动力学模型（Patlak和两组织室模型）评估脑葡萄糖代谢，计算葡萄糖代谢率（MRGlu）。结果suvglu和MRGlu在纤维化前和全脑水平均显著降低，缓解后恢复。SUVgluc统计参数映射发现了多个糖代谢降低的脑区，区域分析证实了这一点，显示SUVgluc呈进行性降低。相关分析证实，与未校正的SUV不同，SUVgluc是MRGlu的可靠替代品。肝脏[18F]FDG摄取在纤维化期间增加，缓解后恢复正常，反映了血糖浓度的变化。结论[18F]FDG PET成像显示肝纤维化改变了肝和脑的葡萄糖代谢，强调了分子成像在未来评估肝和脑代谢相互作用方面的潜力。[18F]动力学模型显示，以suvglu表示的FDG摄取与MRGlu密切相关，支持其作为量化小鼠脑糖代谢的有效替代参数的效用。

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.