Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG), O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET), and [18F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium (18F-fluoromethylcholine, 18F-FCho) PET in discriminating high-grade tumor from RN.