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We assessed the prognostic utility of C-Methionine positron emission tomography (MET-PET) in pediatric high-grade glioma (HGG). Thirty-one children had 62 MET-PET studies. Segmented tumor volumes from co-registered magnetic resonance studies were assessed for concordance with MET-PET uptake using Boolean operations. The tumor volume at diagnosis and treatment failure was assessed relative to MET-PET avid volume. The prognostic impact of MET-PET-delineated non-contrast enhancing tumor (NCET) was assessed. NCET was defined as the region of tumor defined by defined by FLAIR which did not enhance but showed MET-PET avidity. MET-PET concordance varied according to magnetic resonance sequence. MET-PET rarely added to the tumor volume in most cases. The volume of MET-PET with standardized uptake value >3.0 was differentially distributed at diagnosis, post treatment, and at recurrence. The initial MET-PET region overlapped with recurrent tumor in 90% of the cases. When the proportion of tumor which was NCET was >10%, an earlier time to progression (5.8 months; 95% CI, 1-8.2 vs. 10.5 months; 95% CI, 0.9-NR; p = 0.035) was noted. MET-PET delineates regions at increased risk for recurrence and may improve the definition of failure, prognostic assessment, and target definition for radiotherapy. [ABSTRACT FROM AUTHOR]