Borderline Findings in O-(2-[¹⁸F]-Fluoroethyl)-l-Tyrosine PET of Patients with Suspected Glioma Relapse: Role in Clinical Practice

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, <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.