Digital FDG-PET Detects Mutation-Driven Glycolysis in Primary CNS Lymphoma.

[BACKGROUND AND PURPOSE] The relationship between digital F-FDG-PET findings and glucose metabolism-related genetic alterations remains unclear in primary CNS lymphoma (PCNSL). This study aimed to evaluate whether digital FDG-PET can serve as a noninvasive tool to detect mutation-driven glycolytic activity in PCNSL.

[MATERIALS AND METHODS] We retrospectively analyzed the imaging and molecular data of 54 patients with PCNSL (55 lesions). MRI and FDG-PET parameters, including the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), were assessed. Tumor specimens were subjected to histopathologic and genomic evaluations, including the mutation status.

[RESULTS] Among 55 tumors, 34 (61.8%) were examined with digital FDG-PET and 21 (38.2%) with analog F-FDG-PET. In the digital FDG-PET group, -mutant tumors showed statistically higher SUVmax (30.2 ± 9.9) and TBR (6.1 ± 1.5) compared with wild-type tumors (SUVmax: 19.3 ± 7.2, = .006; TBR: 3.5 ± 1.3, < .001). In the analog FDG-PET group, the SUVmax was higher in -mutant tumors ( = .01), whereas the TBR differences were not statistically significant ( = .38). Receiver operating characteristic analysis of TBR in digital FDG-PET yielded an area under the curve of 0.913 (95% CI, 0.954-1.000) with a cutoff value of 4.49, achieving 88% sensitivity and 88% specificity for mutation detection. Multivariate logistic regression identified SUVmax and TBR from digital FDG-PET as independent predictors of mutation status. The transcriptomic analysis confirmed the up-regulation of glycolysis-related genes, including , in -mutant tumors, supporting increased glycolytic activity.

[CONCLUSIONS] Digital FDG-PET may serve as a valuable noninvasive imaging technique to detect mutation-driven enhanced glycolysis in patients with PCNSL.