Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic ¹⁸F-FET PET

Purpose: According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. ¹⁸F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic ¹⁸F-FET PET for the non-invasive prediction of the IDH-mutation status.

Methods: Newly diagnosed WHO grade II-IV glioma patients with MRI and dynamic ¹⁸F-FET PET were included. The ¹⁸F-FET PET parameters mean and maximal tumour-to-background ratio (TBR_mean, TBR_max) and minimal time-to-peak (TTP_min) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas.

Results: Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as ¹⁸F-FET-positive (TBR_max > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBR_max was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0-7.1 vs. 1.1-7.9). Dynamic analysis revealed a significantly shorter TTP_min in IDH-wildtype gliomas; using TTP_min ≤ 12.5 min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTP_min ≤ 12.5 min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001).

Conclusion: A short TTP_min in dynamic ¹⁸F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.