Evaluation of MGMT promoter methylation status in high grade gliomas by 18F-FET PET/MR

Introduction: Objective: O6-Methylguanine-DNA-methyltransferase (MGMT) promoter methylation was an important molecular marker which is shown to be associated with more favorable outcome in high-grade glioma. However, the accurate determination of MGMT methylation status through molecular techniques remains challenging due to various technical limitations, including the unavailability of tumor specimens, exorbitant detection costs, and the intricate nature of intralesional heterogeneity . In order to promote micro-invasive or non-invasive presurgical diagnosis, we aimed to test the feasibility of using the ¹⁸F-FET PET/MR to preoperatively and noninvasively measure the MGMT methylation status.

Methods: Methods: Eight patients were enrolled in this study and the MGMT promoter methylation status was measured by pyrosequencing. ¹⁸F-FET PET/MR scans were performed on the integrated PET/MR 3.0-Tesla system (uPMR 790, United Imaging Healthcare, Shanghai, China) with a 24-channel phase-array head coil. Multi-b value diffusion MR imaging was simultaneously acquired, parameters of distributed diffusion coefficient (DDC) and were calculated using the stretched exponential model. The tumor volumes were delineated by applying SUV-based thresholds (0.4 * SUVmax). We calculated the mean value of PET SUV, DDC, and within the tumor lesion, and compared the group difference between the methylated (N = 4) and the unmethylated (N = 4) group.

Results: Figure 1 shows the ¹⁸F-FET PET image, and DDC maps from eight enrolled patients. The quantitative statistical results were illustrated in Figure 2. The methylated group have higher lesional mean value of SUV (p = 0.031) and (p = 0.008) than the unmethylated group. The value could completely distinguish between these two groups, where the minimum value of the methylated group ( = 0.237) is greater than the maximum value of unmethylated group( = 0.229).

Conclusions: Conclusion: The ¹⁸F-FET PET/MR diffusion imaging is a promising technique for differentiate the MGMT promoter methylation status in glioma noninvasively.