Clinical Utility of [¹⁸F]-Fluciclovine PET/MRI for Differentiating True Progression from Treatment-Related Changes in Patients with Glioblastoma

BACKGROUND AND PURPOSE: Differentiating true progression from treatment-related changes in patients with glioblastoma (GBM) remains a major diagnostic challenge. Amino acid PET tracers such as [^18F]-fluciclovine provide biologically specific information, but clinical real-world validation across institutions is limited. We aimed to evaluate the clinical diagnostic performance of [^18F]-fluciclovine PET/MRI for distinguishing true progression from treatment-related change in patients with presumed GBM progression across 2 academic centers. MATERIALS AND METHODS: In this retrospective, multi-institutional, institutional review board–approved study, we analyzed [^18F]-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. Maximum standardized uptake value (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 index and validation of the previously published diagnostic threshold of 4.66. Subgroup analyses compared diagnostic performance across institutions. RESULTS: 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 2 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 < .01). Combined ROC analysis demonstrated excellent diagnostic performance (area under the curve [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. CONCLUSIONS: [^18F]-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 [^18F]-fluciclovine PET as a biologically specific adjunct to conventional MR imaging for patients with presumed GBM progression.