NONINVASIVE PREOPERATIVE PREDICTION OF MGMT PROMOTER METHYLATION IN GLIOMAS VIA 11C-METHIONINE PET IMAGING AND RADIOMIC TEXTURE ANALYSIS

Abstract

Background: Gliomas represent a highly heterogeneous class of primary brain tumors with molecular characteristics increasingly integrated into their diagnostic and prognostic frameworks. Among these, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has emerged as a key predictor of temozolomide (TMZ) sensitivity and improved patient survival. Concurrently, amino acid positron emission tomography (PET) imaging with ^11C-methionine (^11C-MET) has shown promise for characterizing tumor metabolism and delineating tumor boundaries, potentially providing noninvasive, preoperative insights into glioma biology. Methods: Fifty-six newly diagnosed glioma patients were retrospectively analyzed. All patients underwent ¹¹C-MET PET and MRI prior to surgery, and MGMT promoter methylation status was determined by pyrosequencing. Using a custom software platform, fused PET/MR datasets were evaluated for conventional metabolic parameters—standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and tumor-to-normal tissue ratios (TNRmax, TNRmean)—as well as first-order texture metrics derived from intensity–volume histograms. Statistical comparisons between MGMT promoter-methylated and -unmethylated groups were performed using t-tests, with additional subgroup analyses in WHO Grade 2 tumors. Results: Gliomas harboring MGMT promoter methylation exhibited significantly lower ¹¹C-MET uptake, as indicated by reduced TNRmax and TNRmean values, compared to their unmethylated counterparts. In WHO Grade 2 gliomas, methylated tumors also demonstrated more homogeneous texture parameters, with lower skewness and kurtosis values. These findings suggest that MGMT promoter methylation is associated with reduced metabolic heterogeneity and a more uniform amino acid metabolic profile. Receiver operating characteristic analysis indicated the potential of these texture parameters to noninvasively predict MGMT promoter methylation status preoperatively in WHO Grade 2 patients. Conclusions: Our results highlight the utility of ¹¹C-MET PET imaging, combined with radiomic texture analysis, as a complementary tool for assessing glioma metabolism in relation to MGMT promoter methylation. The observed metabolic differences suggest an avenue for noninvasive prediction of molecular subtype, potentially guiding individualized treatment strategies and patient management. Further studies with larger cohorts and controlled conditions are warranted to validate these findings and explore their prognostic implications.