Imaging biomarkers for detecting IDH mutations and monitoring response to novel targeted therapies: Current insights and future perspectives

Abstract

Isocitrate dehydrogenase (IDH) mutant gliomas represent a unique molecular subset of gliomas with distinct metabolic and microstructural characteristics. The recent approval of targeted IDH inhibitors marks a significant advancement in glioma therapy, thereby necessitating robust, quantitative methods for noninvasive assessment of treatment response. This review provides an overview of advanced multiparametric imaging techniques—including proton MR spectroscopy, diffusion and perfusion MRI, amide proton transfer imaging, and amino acid positron emission tomography imaging—and their role in detecting IDH-mutations and monitoring therapeutic response to IDH inhibitors. Special emphasis is placed on metabolic imaging of the oncometabolite D-2-hydroxyglutarate (2-HG), a hallmark signature of IDH-mutant gliomas, and how its quantification serves as a surrogate biomarker for diagnosis and treatment monitoring. We also highlight the potential of advanced diffusion MRI-based models, which capture microstructural alterations beyond conventional apparent diffusion coefficient metrics. Some limitations of these techniques in clinical translation are also considered, along with future directions to integrate them into prospective clinical trials.