Purpose <p>PET using the radiolabeled amino acid <i>O</i>-(2-[¹⁸F]-fluoroethyl)-L-tyrosine ([¹⁸F]FET) has considerable clinical value for follow-up evaluation of central nervous system tumors in children and adolescents. As medical procedures must be justified socio-economically, we determined cost-effectiveness of [¹⁸F]FET PET for identification of treatment-related changes.</p> Methods <p>We analyzed clinical data from two different studies that assessed the value of FET PET to differentiate between brain and spinal tumor relapse and treatment-related changes in children and adolescents. Cost calculation was based on the German statutory health insurance system perspective. Due to subtle differences in the diagnostic approach of the studies, two separate clinical scenarios including 80 patients with 105 lesions were considered: Decision tree model 1 determined cost-effectiveness of simultaneous [¹⁸F]FET PET and MRI in comparison to MRI alone to identify treatment-related changes. Decision tree model 2 determined cost-effectiveness of [¹⁸F]FET PET alone to identify treatment-related changes when routine MRI findings were suspicious for tumor relapse. Deterministic and probabilistic sensitivity analyses tested the robustness of the results.</p> Results <p>Model 1 revealed that the rate of identified treatment-related changes increased by 52% when adding [¹⁸F]FET PET to MRI, resulting in costs of €3,314.51 for each additional correctly identified lesion with treatment-related changes by [¹⁸F]FET PET that MRI would have misclassified. Model 2 revealed that [¹⁸F]FET PET correctly identified treatment-related changes in 90% of lesions when routine MRI findings were suspicious for tumor relapse, resulting in costs of €1,740.37 for each lesion.</p> Conclusion <p>Integrating [¹⁸F]FET PET in the follow-up of in children and adolescents with brain and spinal tumor may help improving patient care at acceptable costs.</p>