Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

Area of Science:

• Neuro-oncology
• Metabolic imaging
• Molecular diagnostics

Background:

• Preclinical studies suggest metabolic reprogramming in isocitrate dehydrogenase (IDH) mutated tumors, with decreased glycolytic gene expression.
• Investigating metabolic alterations in gliomas is crucial for understanding tumor behavior and developing targeted therapies.

Purpose of the Study:

• To noninvasively assess metabolic differences in IDH-mutant versus IDH wild-type gliomas using magnetic resonance (MR) spectroscopy.
• To evaluate lactate and Cr concentrations and intracellular pH in glioma patients.

Main Methods:

• Utilized 1H/phosphorus 31 (31P) MR spectroscopy in 30 glioma patients (WHO grades II-IV).
• Acquired 3D 31P chemical shift imaging and 1H single-voxel spectroscopy.
• Quantified absolute metabolite concentrations and determined intracellular pH.

Main Results:

• IDH-mutant gliomas exhibited significantly lower lactate concentrations and lactate/Cr ratios compared to IDH wild-type gliomas.
• Intracellular pH was near-normal in IDH-mutant gliomas.
• 1p/19q codeletion showed a codependent effect with IDH mutations, leading to lower lactate levels in WHO grades II and III.

Conclusions:

• Provided indirect evidence for metabolic reprogramming in IDH-mutant gliomas.
• Demonstrated significantly lower lactate levels and near-normal intracellular pH in IDH-mutant gliomas compared to IDH wild-type gliomas.
• Highlighted the potential of MR spectroscopy for noninvasive metabolic characterization of gliomas.