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

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Key points: • 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.

Keywords: Glioma; MGMT promoter methylation; Molecular typing; Perfusion magnetic resonance imaging; Positron-emission tomography.