Distinguishing Progression from Pseudoprogression in Glioblastoma Using ¹⁸F-Fluciclovine PET

Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. ¹⁸F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of ¹⁸F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative ¹⁸F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUV_max (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUV_max cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUV_max cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: ¹⁸F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of ¹⁸F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with ¹⁸F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.