# Potential of Preoperative 11C-Methionine Positron Emission Tomography in Predicting EGFR Alterations and CDKN2A/B Homozygous Deletion in Diffuse Astrocytic Gliomas

## TL;DR

This study explores how PET scans can predict genetic changes in brain tumors before surgery, potentially guiding treatment decisions.

## Contribution

The study identifies specific PET tracer uptake patterns that correlate with EGFR and CDKN2A/B alterations in astrocytic gliomas.

## Key findings

- Tumors with IDH mutations, ATRX mutations, or loss had lower T/N ratios on MET-PET and FDG-PET.
- CDKN2A/B homozygous deletions and EGFR alterations correlated with higher MET-PET T/N ratios.
- FDG-PET T/N ratios were higher in tumors with NF1 mutations or loss.

## Abstract

Objective

L-methyl-11C-methionine (MET)- and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) are used to detect gliomas. However, the efficacy of MET-PET and FDG-PET in detecting gene alterations in gliomas remains unclear. Therefore, in this study, we evaluated the relationship between genetic alterations and PET tracer uptake in diffuse astrocytic glioma.

Methods

Thirty-two patients who had been newly diagnosed with astrocytic gliomas at Kagoshima University and Kyushu University and had undergone MET-PET and FDG-PET were enrolled. They underwent analysis of glioma-related gene expression using a customized 48-gene panel.

Results

The tumors identified in this study were classified as follows: glioblastomas, isocitrate dehydrogenase (IDH) wildtype (n = 15); astrocytic glioma, IDH-mutant, World Health Organization (WHO) grade 4 (n = 2); astrocytic glioma, IDH-mutant, WHO grade 3 (n = 4); astrocytic glioma, IDH-mutant, WHO grade 2 (n = 7); and diffuse astrocytic glioma, not elsewhere classified (n = 4). Astrocytic tumors with IDH mutations, ATRX mutations, and/or loss of function (mut/loss) had a significantly lower tumor-to-normal tissue (T/N) ratio on the MET-PET and FDG-PET images compared with those without these alterations. Astrocytic tumors with CDKN2A/B homozygous deletions (HD), EGFR mutation and/or amplification (mut/amp), or PTEN mut/loss had a significantly higher T/N ratio on the MET-PET images compared with those without these alterations. Astrocytic tumors with NF1 mut/loss had a significantly higher T/N ratio on their FDG-PET images compared with those without these alterations. The cut-off T/N ratio for the MET-PET images for the identification of EGFR mut/amp was 4.50 (sensitivity: 95%; specificity: 56%, AUC: 0.77), and that for detecting CDKN2A/B HDwas 2.32 (sensitivity: 72%; specificity: 86%; AUC: 0.85).

Conclusion

These findings from our small, retrospective cohort study suggest that MET-PET and FDG-PET are potentially valuable approaches for preoperatively predicting the molecular status of gliomas, particularly for assessing tumors with EGFR mut/amp and CDKN2A/B HD. Preoperative genetic alteration prediction in astrocytic gliomas based on PET tracer uptake may provide accurate information for patients and inform clinical decision-making. Multicenter prospective trials are essential.