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. F-18-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 F-18-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 F-18-FET PET were included. The F-18-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) 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 F-18-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax 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 TTPmin in IDH-wildtype gliomas; using TTPmin <= 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, TTPmin <= 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 TTPmin in dynamic F-18-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.