[¹⁸F]FET uptake in diffuse lower-grade IDH-mutant glioma correlates with glioma-related epilepsy

Diffuse lower-grade glioma (DLGG), i.e. WHO grade 2 and 3 tumors, frequently manifests with epileptic seizures, significantly affecting quality of life. While [¹⁸F]FET PET is routinely used to assess glioma metabolism, differences between patients with and without glioma-related epilepsy have not yet been assessed systematically. The objective of this study was to assess whether preoperative [¹⁸F]FET PET uptake is associated with epileptic seizures at initial presentation in patients with DLGG.

This retrospective study included 121 patients with DLGG with preoperative [¹⁸F]FET PET (2015-2025). [¹⁸F]FET uptake parameters were determined in patients with measurable disease according to PET RANO 1.0 criteria. Seizure status was assessed exclusively for seizures occurring before surgery. Statistical analyses included Fisher's exact test, Mann-Whitney U test, and multivariable logistic regression.

Seventy-eight patients (64%) demonstrated measurable disease in [¹⁸F]FET, of whom 57 (73%) presented with epileptic seizures compared to 17 (40%) in the no-uptake group (p < 0.001). In the measurable disease group, those with seizures exhibited significantly higher median TBR_max (3.02; IQR 2.35-4.00) and TBR_mean (2.2; IQR 1.8-2.5) values than those without seizures (TBR_max 2.4; IQR 2.00-3.16, TBR_mean 1.9; IQR 1.7-2.2). The tumor location did not account for the observed association between [¹⁸F]FET uptake and seizures (p > 0.05). In multivariable analyses, [¹⁸F]FET uptake remained independently associated with preoperative seizures (adjusted OR 2.86, 95% CI 1.18-7.07; p = 0.020).

These findings demonstrate an association between [¹⁸F]FET uptake and glioma-related epilepsy in DLGG. Further research on amino acid transporter expression and glutamatergic pathways may elucidate underlying mechanisms.