Purpose: This retrospective study aimed to correlate ¹⁸F-FDG uptake on PET/CT with isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutation in patients with cerebral gliomas. Hierarchical interactions between factors affecting overall survival (OS) were also examined. Methods: In 59 patients with glioma, the ratio of the SUVmax of a glioma to the SUVmean of the contralateral cortex (G/C ratio) on ¹⁸F-FDG PET/CT and the presence of IDH1 mutation were correlated. The prognostic value of clinicopathologic factors and G/C ratio for OS were assessed using a Cox proportional hazards model and classification and regression tree models. Results: The mean G/C ratio of IDH1-mutant tumors was significantly lower than that of IDH1 wild-type tumors (0.73 vs 1.14, P = 0.004). In multivariate analysis, IDH1-mutant and G/C ratio were significant for OS. The classification and regression tree modeling identified 3 risk groups for OS (group 1: IDH1 mutant [hazard ratio, 0.2]; group 2: G/C ratio ≤0.8 with IDH1 wild type [hazard ratio, 0.83]; group 3: G/C ratio >0.8 with IDH1 wild type [hazard ratio, 1.9]) (overall P < 0.001). The mean OS was 37.0 months in group 1, 28.6 months in group 2, and 20.7 months in group 3, respectively, showing significant differences among the groups (group 1 vs group 2: P = 0.023, group 2 vs group 3: P = 0.049, group 1 vs group3: P < 0.001). Conclusions: ¹⁸F-FDG uptake of IDH1-mutant gliomas was significantly lower than that of IDH1 wild-type gliomas. IDH1 mutation was the most important factor in identifying patients with the best prognosis, whereas increased ¹⁸F-FDG uptake provided additional prognostic information for predicting poor OS among patients with IDH1 wild-type gliomas.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib, a multi-kinase inhibitor, is the first-line therapy for advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity and the development of resistance. Although various amino acids have been shown to contribute to cancer initiation and progression, little is known about the effects of histidine, a dietary essential amino acid that is partially taken up via histidine/large neutral amino acid transporter (LAT1), on cancer cells. In this study, we evaluated the effects of histidine on HCC cells and sensitivity to sorafenib. Remarkably, we found that exogenous histidine treatment induced a reduction in the expression of tumor markers related to glycolysis (GLUT1 and HK2), inflammation (STAT3), angiogenesis (VEGFB and VEGFC), and stem cells (CD133). In addition, LAT1 expression was downregulated in HCC tumor regions with high expression of GLUT1, CD133, and pSTAT3, which are known to induce sorafenib resistance. Finally, we demonstrated that combined treatment with sorafenib and histidine could be a novel therapeutic strategy to enhance the sensitivity to sorafenib, thereby improving long-term survival in HCC.

Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores ¹¹C-acetate PET as an imaging technique for detecting reactive astrogliosis. Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated ¹¹C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and MCT1 expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of ¹¹C-acetate uptake beyond MRI and prognosis. Elevated ¹¹C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of ¹¹C-acetate uptake beyond contrast-enhanced MRI was associated with worse prognosis. Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of ¹¹C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.