MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study.

Abstract

To investigate the effects of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status of gliomas on O-(2-18F-fluoroethyl)-L-tyrosine ([18F]FET) uptake and cerebral blood flow (CBF) of arterial spin labeling (ASL), evaluated by hybrid PET/MR. Stereotactic biopsy was used to validate the findings. A set of whole tumor and reference volumes of interest (VOIs) based on PET/FLAIR imaging were delineated and transferred to the corresponding [18F]FET PET and CBF maps in 57 patients with newly diagnosed gliomas. The mean and max tumor-to-brain ratio (TBR) and normalized CBF (nCBF) were calculated. The predictive efficacy of [18F]FET PET and CBF in determining MGMT promoter methylation status of glioma were evaluated by whole tumor analysis and stereotactic biopsy. The correlation between PET/MR parameters and MGMT promoter methylation were analyzed using histological specimens acquired from multiple stereotactic biopsies. Based on the analysis of whole tumor volume and biopsy site, TBRmean, TBRmax, nCBFmean, and nCBFmax showed no statistically significant differences between gliomas with and without MGMT promoter methylation (all p > 0.05). Furthermore, stereotactic biopsy demonstrated that TBRmean, TBRmax, nCBFmean, and nCBFmax showed no correlation with MGMT promoter methylation (r = -0.117, p = 0.579; r = -0.161, p = 0.443; r = -0.271, p = 0.191; r = -0.300, p = 0.145; respectively). MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. Stereotactic biopsy validates it and further reveals there is no correlation of [18F]FET PET uptake and CBF with the percentages of MGMT promoter methylation. • Based on whole tumor VOI assessment, MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. • For WHO grade IV glioblastomas, [18F]FET PET and ASL parameters based on hybrid PET/MR fail to predict the MGMT promoter methylation status. • Stereotactic image-based histology reveals that there is no correlation of [18F]FET PET uptake and CBF with the status and percentages of MGMT promoter methylation in gliomas.