Paired [18F]FDOPA and [18F]FDG PET Shows Complementary Prognostic Associations at Recurrence in IDH-Wildtype Glioblastoma

Background/Objectives: Prognostic PET biomarkers in glioblastoma remain mostly as a single tracer and poorly characterized at recurrence. We investigated whether paired [18F]FDOPA/[18F]FDG PET captures complementary metabolic information associated with survival in IDH-wildtype glioblastoma. Methods: Sixty-five consecutive patients underwent paired [18F]FDOPA/[18F]FDG PET/MR at baseline and/or recurrence. Survival was analyzed from baseline PET/MR (OS1, n = 36) and recurrence PET/MR (OS2, n = 55); longitudinal analyses used the paired subgroup (n = 26). FDOPA and FDG tumor masks were independently segmented within a FLAIR-derived tumor box, and metrics were extracted from tracer-specific masks, their intersection, and their union. Metrics significant in Kaplan–Meier or univariable Cox analyses were tested in adjusted Cox models. Benjamini–Hochberg false discovery rate correction was used as a sensitivity analysis for the continuous Cox screening tests. Results: In exploratory screening, prognostic associations were sparse at baseline and more prominent at recurrence. At OS2, three metrics remained independently associated with survival after adjustment: the FDOPA/FDG union-domain SUVmeanunion ratio (HR, 1.50; p = 0.0168), MTVinter (HR, 1.63; p = 0.0154), and MTVDOPA (HR, 1.58; p = 0.0191). The SUVmeanunion ratio and MTVDOPA showed limited correlation, suggesting complementary information. Their integration into IR-MTVDOPA, defined as FDOPA/FDG SUVmeanunion ratio × log(MTVDOPA), showed higher apparent OS2 discrimination (HR, 1.73; log-rank p = 0.0001; C-index, 0.730; bootstrap .632-corrected C-index, 0.684; 12-month AUC, 0.863). Conclusions: In this exploratory single-center cohort, paired [18F]FDOPA/[18F]FDG PET showed prognostic associations at recurrence. Inter-tracer intensity balance and metabolic tumor burden provided partially complementary survival information, and their exploratory integration showed higher apparent discrimination. External validation is required before clinical implementation.