Radiolabeled amino acids were introduced in 1982 as suitable PET tracers in brain tumors [17]. The use of amino acids is based on an increased amino acid utilization in cancer cells, which is known to play a pivotal role in cell proliferation, as well as in extracellular matrix synthesis. For this purpose, a variety of radiolabeled amino acids, like ¹¹C-MET and aromatic amino acid analogs, like ¹⁸F-fluorotyrosine (^18F-TYR), ¹⁸F-FET, ¹⁸F-fluoromethyltyrosine (¹⁸F-FMT), and ¹⁸F-DOPA, have been studied. Active amino acid transport is upregulated in the cell membranes of tumor cells, regardless of the phase of the cell cycle, thus not representing a limiting factor for successful PET imaging. High-contrast images can be acquired due to high amino acid uptake in tumors and low uptake in normal brain tissue compared to FDG. Possible problem may be caused by unspecific increase of amino acid uptake due to damage of the blood-brain barrier [18]. Methionine uptake correlates not only with cell proliferation but also with microvessel density, suggesting the possibility of mapping tumor neovascularization. The accumulation of MET in macrophage is irrelevant overcoming the limitation of FDG due to uptake in inflammatory process. The uptake of ¹¹C-MET gradually increased with age until 20 years especially in the frontal lobes and cerebellum, possibly reflecting high activity of the neutral amino acid transporter and brain protein synthesis correlated with brain metabolism. The highest uptake is found in the cerebellum and occipital cortex, lower in the white matter [19]. The clinical application of ¹¹C-MET has been proved both for tumor diagnosis (tumor detection and characterization, extent for treatment planning, biopsy guidance) and for treatment evaluation (therapy monitoring, detection of recurrent/persistent disease). The specificity of MET for brain tumor evaluation is generally high (85–100 %), and tumor/background radio superior to 1.5 is considered indicative of tumor. The use of this radiopharmaceutical is particularly interesting in suspicious low-grade glioma that cannot easily identify with FDG PET. The MET uptake may be overlying among grades I and II glioma and grades III and IV; however, it may provide a prognostic index in patients with low-grade glioma [20]. Furthermore, ¹¹C-MET is the radiopharmaceutical of choice for PET-guided biopsy. The distribution of MET in brain lesion reflects the histological heterogeneity of the tumor, indicating more accurately the areas to be biopsied [21]. It has been shown that MET-guided biopsy reduces the number of attempts to obtained diagnostic samples, providing a more sensitive mark compared to FDG. Another crucial point in the management of brain tumor is the distinction between recurrence and post-therapy changes. The MET PET has been shown to be superior to FDG (sensitivity 100 %, specificity 72 %, PPV 81 %, NPV 100 %) in differentiating viable tumor from radiation injury [22–24]. Infrequently a mild MET uptake may be observed due to the proliferation of glial cell that may be present after radiation therapy. To increase the diagnostic performance, it has been suggest that tumor-background ratio superior to 1.5–2 should be considered indicative of tumor presence. ¹¹C-methionine is probably the tracer of choice at this time, in terms of its sensitivity, specificity, and accuracy, but its major disadvantage is the short half-life of ¹¹C (20 min) which implies on-site cyclotron. ¹⁸F-amino acid has been shown comparable results, overcoming the problem of radiopharmaceutical production [25]. ¹⁸F-fluoro-ethyl-tyrosine (¹⁸F-FET) is an artificial amino acid taken up into upregulated tumoral cells but not incorporated into proteins (contrary to natural amino acids such as ¹¹C-methionine). ¹⁸F-FET PET has excellent performance for the diagnosis of brain tumor and glioma in the initial evaluation of newly diagnosed brain lesions. Initial comparison studies demonstrated that ¹⁸F-FET uptake ratios correlated with ¹¹C-methionine uptake but with a lesser uptake by inflammatory cells, allowing a better discrimination between infectious and tumoral lesions or between tumor recurrence and radionecrosis [26]. Among other applications, ^18F-FET PET has shown value in the diagnosis of brain tumor recurrence after initial surgery or radiotherapy and for directing biopsy or radiosurgery. Furthermore early changes in ¹⁸F-FET uptake have been suggested as a surrogate to predict tumor response to treatment and prognosis. ¹⁸F-DOPA is also an amino acid analog which is taken up in normal brain by the neutral amino acid transporter. The highest radiopharmaceutical uptake in tumor and cerebellum generally occurred between 10 and 30 min after injection, while the uptake in the striatum reaches the peak until 50 min after injection. ¹⁸F-FDOPA has a sensitivity of 96 % and a specificity of 43 %, with an overall accuracy of 83 % for the detection of primary brain tumors [27]. Compared to FDG, ¹⁸F-DOPA has shown a better accuracy with a higher sensitivity and a similar specificity, allowing an excellent visualization of both high-grade and low-grade tumors. The contrast between tumor and normal tissue is higher than that with ¹⁸F-FDG because of the low ¹⁸F-DOPA uptake in normal brain tissue. Tripathi and colleagues [28] in a series of 15 patients demonstrated that ¹⁸F-DOPA is superior both to FLT and FDG for detection of primary and recurrent low-grade gliomas. ¹⁸F-DOPA should demonstrate good feasibility in detecting local recurrence and residual tumor not clearly seen on MR alone; however, the evaluation of this aspect is still limited in literature.