PT - JOURNAL ARTICLE AU - Langen, Karl-Josef AU - Stoffels, Gabriele AU - Filss, Christian P. AU - Kocher, Martin AU - Lerche, Christoph AU - Sabel, Michael AU - Rapp, Marion AU - Noltemeier, Hosai AU - Werner, Jan-Michael AU - Ceccon, Garry AU - Wollring, Michael M. AU - Rosen, Jurij AU - Steinbach, Joachim P. AU - Hattingen, Elke AU - Weinzierl, Martin R. AU - Stoffel, Michael AU - Clusmann, Hans AU - Shah, N. Jon AU - Mottaghy, Felix M. AU - Galldiks, Norbert AU - Lohmann, Philipp TI - Borderline Findings in <em>O</em>-(2-[<sup>18</sup>F]-Fluoroethyl)-<span class="sc">l</span>-Tyrosine PET of Patients with Suspected Glioma Relapse: Role in Clinical Practice AID - 10.2967/jnumed.124.268768 DP - 2025 Jan 16 TA - Journal of Nuclear Medicine PG - jnumed.124.268768 4099 - http://jnm.snmjournals.org/content/early/2025/01/16/jnumed.124.268768.short 4100 - http://jnm.snmjournals.org/content/early/2025/01/16/jnumed.124.268768.full AB - One of the most common clinical indications for amino acid PET using the tracer O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) is the differentiation of tumor relapse from treatment-related changes in patients with gliomas. A subset of patients may present with an uptake of 18F-FET close to recommended threshold values. The goal of this study was to investigate the frequency of borderline cases and the role of quantitative 18F-FET PET parameters in this situation. Methods: We retrospectively identified 439 patients with pretreated gliomas who underwent 18F-FET PET for suspected tumor relapse and in whom the final diagnoses were confirmed by histopathology (n = 175) or clinical course (n = 264). Two experienced nuclear medicine physicians, masked to the final diagnoses, evaluated visually the PET scans by consensus. The findings were classified into 3 categories: clearly positive findings, borderline findings, or clearly negative findings. The diagnostic performance of established 18F-FET PET parameters (i.e., tumor-to-brain ratio [TBR], time-to-peak ratio, slope, intercept) was evaluated separately for these 3 groups using receiver operating characteristics analyses. Results: In the visual analysis, 18F-FET uptake was classified as clearly negative in 67 patients (15%), clearly positive in 234 patients (53%), and borderline in 136 patients (31%), with averaged mean TBR values of 1.5, 2.3, and 1.9, respectively. Receiver operating characteristics analysis showed a high accuracy for TBR values in patients rated as clearly positive or negative in visual rating (area under curve [AUC], 0.84–0.86), whereas the diagnostic performance of TBR values in borderline cases according to visual analysis was significantly lower (AUC, &lt;0.60). Using TBR values ± 10% above or below the cutoff values increased the AUC by approximately 10% (AUC, 0.82–0.84). Conclusion: A considerable number of patients may present with borderline findings in 18F-FET PET. In these patients, quantitative parameters should be used with caution for decision-making. The use of TBR values above or below the range of the cutoff values ±10% may increase the reliability of quantitative parameters to differentiate between tumor relapse and treatment-related changes.