Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of ¹¹C-methionine (MET) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors.

We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values.

In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027).

MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.