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

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.

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.

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 SUV_mean^union ratio (HR, 1.50; p = 0.0168), MTV^inter (HR, 1.63; p = 0.0154), and MTV^DOPA (HR, 1.58; p = 0.0191). The SUV_mean^union ratio and MTV^DOPA showed limited correlation, suggesting complementary information. Their integration into IR-MTV^DOPA, defined as FDOPA/FDG SUV_mean^union ratio × log(MTV^DOPA), 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).

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.