{"doi":"10.3174/ajnr.a9120","title":"Clinical Utility of [ <sup>18</sup> F]-Fluciclovine PET/MRI for Differentiating True Progression from Treatment-Related Changes in Patients with Glioblastoma","abstract":"<h3>ABSTRACT</h3> <h3>BACKGROUND AND PURPOSE:</h3> Differentiating true progression from treatment-related changes in patients with glioblastoma (GBM) remains a major diagnostic challenge. Amino acid PET tracers such as [F18]-Fluciclovine provide biologically specific information, but clinical real-world validation across institutions is limited. We aimed to evaluate the clinical diagnostic performance of [F18]-Fluciclovine PET/MRI for distinguishing true progression from treatment-related change in patients with presumed GBM progression across 2 academic centers. <h3>MATERIALS AND METHODS:</h3> In this retrospective, multi-institutional, IRB-approved study, we analyzed [F18]-Fluciclovine PET/MRI scans performed in patients with presumed GBM progression. All PET/MRI examinations were clinically indicated and performed as part of routine standard-of-care imaging. Clinical classification was based on histopathology or imaging and clinical follow-up. SUVmax was measured in enhancing lesions. Group comparisons were assessed with Mann–Whitney U tests. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis, including derivation of an optimal cutoff using Youden’s index and validation of the previously published diagnostic threshold of 4.66 (Nabavizadeh <i>et al</i>.). Subgroup analyses compared diagnostic performance across institutions. <h3>RESULTS:</h3> Thirty-six patients with presumed GBM progression (Institution 1, n = 17; Institution 2, n = 19) provided 22 examinations classified as true tumor progression and 14 as treatment-related change. There were no significant differences in clinical or demographic study population characteristics between the two institutions. SUVmax was significantly higher in true tumor progression than in treatment-related change (median [interquartile range], 8.73 [5.86 -10.83] versus 3.71 [1.70 -4.67], p&lt; .01). Combined ROC analysis demonstrated excellent diagnostic performance (AUC=0.90; 95% CI, 0.79–0.98). The optimal threshold of 5.7 yielded 86% sensitivity (0.70–0.99) and 86% specificity (0.64–0.99). Applying the published threshold of 4.66 produced similar results (AUC=0.90), with 91% sensitivity (0.71–0.99) and 71% specificity (0.42–0.92). A stratified analysis demonstrated comparable diagnostic performance across both institutions. <h3>CONCLUSIONS:</h3> [F18]-Fluciclovine PET/MRI demonstrated high diagnostic accuracy for differentiating true GBM progression from treatment-related changes, with consistent SUVmax thresholds across 2 institutions. These findings support the generalizability of [F18]-Fluciclovine PET as a biologically specific adjunct to conventional MR imaging for patients with presumed GBM progression. 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