We evaluated the diagnostic accuracy of PET with L-methyl-11 Cmethionine ( 11 C-MET) for the differentiation of recurrent brain tumors from radiation necrosis. Methods: Seventy-seven patients who had been previously treated with radiotherapy after primary treatment for metastatic brain tumor (n 5 51) or glioma (n 5 26) were studied to clarify the diagnostic performance of 11 C-MET PET in differentiating between recurrent brain tumors and radiation necrosis. A total of 88 PET scans with 11 C-MET were obtained; sometimes more than one scan was obtained when there was an indication of recurrent brain tumor or radiation necrosis. A definitive diagnosis was made on the basis of pathologic examination for recurrent brain tumors and on the basis of pathologic examination or clinical course for radiation necrosis. Several indices characterizing the lesions were determined; these included mean and maximum standardized uptake values (SUV mean and SUV max , respectively) and the ratios of lesion uptake to contralateral normal frontal-lobe gray matter uptake corresponding to the SUV mean and the SUV max (L/N mean and L/N max , respectively). Receiver-operating-characteristic (ROC) curve analysis was used to determine the optimal index of 11 C-MET PET and cutoff values for the differential diagnosis of tumor recurrence and radiation necrosis. Results: The values of each index of 11 C-MET PET tended to be higher for tumor recurrence than for radiation necrosis. There were significant differences between tumor recurrence and radiation necrosis in all of the indices except for the L/N max for glioma. ROC analysis indicated that the L/N mean was the most informative index for differentiating between tumor recurrence and radiation necrosis. An L/N mean of greater than 1.41 provided the best sensitivity and specificity for metastatic brain tumor (79% and 75%, respectively), and an L/N mean of greater than 1.58 provided the best sensitivity and specificity for glioma (75% and 75%, respectively). Conclusion: 11 C-MET PET can provide quantitative values to aid in the differentiation of tumor recurrence from radiation necrosis, although these values do not appear to be absolute indicators. Quantitative analysis of 11 C-MET PET data may be helpful in managing irradiated brain tumors. Pri mary treatment of brain tumors usually consists of a combination of surgery, radiotherapy, and chemotherapy. Postradiation reactions in the central nervous system can occur after conventional radiotherapy and stereotactic radiosurgery (SRS) (1). Radiation necrosis after the aggressive use of irradiation for malignant brain tumors appears to be more common than previously estimated (2). Differentiating between recurrent brain tumors and radiation necrosis, however, is often difficult with conventional diagnostic imaging techniques, such as MRI (3). This is an unsolved issue in managing irradiated brain tumors.Recently, several imaging modalities, such as MR spectroscopy (4-6), SPECT with 201 Tl-chloride ( 201 Tl) (7), and PET with various radiotracers (...