Glioma Imaging by O-(2-18F-Fluoroethyl)-L-Tyrosine PET and Diffusion-Weighted MRI and Correlation With Molecular Phenotypes, Validated by PET/MR-Guided Biopsies.

Ye Cheng,Geng Xu,Yukui Wei,Lixin Xu,Xinru Xiao,Qingtang Lin,Jie Lu,Hongwei Yang,Zhigang Qi,Leiming Wang,Shuangshuang Song,Jie Ma,Tingting Sun,Zeliang Hu,Jie Bai,Yang An

doi:10.3389/fonc.2021.743655

Abstract

Gliomas exhibit high intra-tumoral histological and molecular heterogeneity. Introducing stereotactic biopsy, we achieved a superior molecular analysis of glioma using O-(2-18F-fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI). Patients underwent simultaneous DWI and FET-PET scans. Correlations between biopsy-derived tumor tissue values, such as the tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC)/exponential ADC (eADC) and histopathological diagnoses and those between relevant genes and TBR and ADC values were determined. Tumor regions with human telomerase reverse transcriptase (hTERT) mutation had higher TBR and lower ADC values. Tumor protein P53 mutation correlated with lower TBR and higher ADC values. α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX) correlated with higher ADC values. 1p/19q codeletion and epidermal growth factor receptor (EGFR) mutations correlated with lower ADC values. Isocitrate dehydrogenase 1 (IDH1) mutations correlated with higher TBRmean values. No correlation existed between TBRmax/TBRmean/ADC/eADC values and phosphatase and tensin homolog mutations (PTEN) or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Furthermore, TBR/ADC combination had a higher diagnostic accuracy than each single imaging method for high-grade and IDH1-, hTERT-, and EGFR-mutated gliomas. This is the first study establishing the accurate diagnostic criteria for glioma based on FET-PET and DWI.

Highlights

Gliomas are among the most common and severe primary intracranial tumors in humans, glioblastoma (GBM) (WHO, grade IV)
Eleven patients with newly diagnosed supratentorial gliomas who underwent hybrid 18F-FET-positron emission tomography (PET)/MRI and diffusion-weighted magnetic resonance imaging (DWI) prior to biopsy from January 2019 to December 2019 were included in this study
The correlations of the mutation status of the genetic markers with tobackground ratio (TBR) and apparent diffusion coefficient (ADC)/exponential ADC (eADC) are shown in Figures 3–5, respectively

Summary

Introduction

Gliomas are among the most common and severe primary intracranial tumors in humans, glioblastoma (GBM) (WHO, grade IV). Several molecular markers, including isocitrate dehydrogenase 1 (IDH1), epidermal growth factor receptor (EGFR), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, telomerase reverse transcriptase (TERT), 1p/19q codeletion, phosphatase and tensin homolog (PTEN), and a-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX), have been shown to be glioma prognostic factors [4,5,6,7], and their threshold values have been validated clinically. Some of these factors are used as a primary reference for post-operative therapy selection [8]

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Conclusion