The aim is to explore the concept of photopenic defects in newly diagnosed glioma patients with the 2 widely used C-MET and F-FDOPA PET amino acid tracers. Thirty-two C-MET and 26 F-FDOPA PET scans with amino acid PET-negative gliomas were selected in this European multicentric study. Of these gliomas, 16 C-MET and 10 F-FDOPA PET scans with photopenic defects were identified, exhibiting lower mean tumor-to-background ratio as compared with isometabolic gliomas (P < 0.001). Gliomas with photopenic defects had no different progression-free survival than isometabolic gliomas in the whole population (P = 0.40), but shorter progression-free survival in the subgroup of World Health Organization grade II IDH-mutant astrocytomas (35 vs 68 months; P = 0.047).