In vivo proton MR spectroscopy reveals alterations in cysteine metabolism in human gliomas

Motivation: The cysteine metabolic pathway has been previously shown to be involved in the pathogenesis of gliomas and upregulated in glioblastomas relative to lower-grade gliomas. Goal(s): The aim of this study was to investigate cysteine metabolism in glioma patients in vivo. Approach: Edited 1H-MRS targeting cystathionine was performed in twenty-nine patients with lesions radiographically consistent with gliomas. Results: Cystathionine, glutamate, and glutathione were found to be higher in grade IV than in grade II/III tumors. Cystathionine and glutamate concentrations were also positively correlated with glutathione concentrations. Impact: The measurement of dysregulated cysteine metabolism by 1H-MRS could provide a non-invasive biomarker for monitoring treatments that target this pathway, including cysteine depletion. High levels of cystathionine in the absence of 2HG could be a marker of IDH-wildtype glioblastoma.