# Cortical Origin-Dependent Metabolic and Molecular Heterogeneity in Gliomas: Insights from 18F-FET PET

## TL;DR

This study shows that gliomas from different brain regions have distinct metabolic activity, molecular features, and survival rates, as revealed by PET imaging and genetic analysis.

## Contribution

The study reveals cortical origin-dependent metabolic and molecular heterogeneity in gliomas, linking imaging data with genetic markers and survival outcomes.

## Key findings

- GBMs from mesocortex had longer survival than those from neocortex.
- TERT promoter mutations varied between cortical regions for GBMs and WHO grade 3 gliomas.
- No molecular differences were found in WHO grade 2 gliomas between cortical regions.

## Abstract

Objectives: The objective of this study is to explore the potential variations in metabolic activity across gliomas originating from distinct cortical regions, as assessed by O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET). Also, this study seeks to elucidate whether these metabolic disparities correlate with the molecular characteristics and clinical prognoses of the tumors. Specifically, this research aims to determine whether variations in 18F-FET PET uptake are indicative of underlying genetic or biochemical differences that could influence patients’ outcomes. Methods: The researchers retrospectively included 107 patients diagnosed with gliomas from neocortex and mesocortex, all of whom underwent hybrid PET/MR examinations, including 18F-FET PET and diffusion weighted imaging (DWI), prior to surgery. The mean and maximum tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC) values were calculated based on whole tumor volume segmentations. Comparisons of TBR, ADC values, and survival outcomes were performed to determine statistical differences between groups. Results: Among glioblastomas (GBMs, WHO grade 4) originating from the two cortical regions, there was a significant difference in the human Telomerase Reverse Transcriptase (TERT) promoter mutation rate, while no difference was observed in O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status. For WHO grade 3 gliomas, significant differences were found in the TERT promoter mutation rate and the proportion of 1p/19q co-deletion between the two cortical regions, whereas no difference was noted in MGMT methylation status. For WHO grade 2 gliomas, no molecular phenotypic differences were observed between the two cortical regions. In terms of survival, only GBMs originating from the mesocortex demonstrated significantly longer survival compared to those from the neocortex, while no statistically significant differences were found in survival for the other two groups. Conclusions: Gliomas originating from different cortical regions exhibit variations in metabolic activity, molecular phenotypes, and clinical outcomes.