<sup>18</sup>F-Fluciclovine for Detection of Recurrent Brain Metastases After Radiation Therapy: Image Interpretation Criteria and Diagnostic Performance From the PURSUE Study.

Kotecha, Rupesh; Chiang, Veronica; Tom, Martin C; Parent, Ephraim; Nabavizadeh, Ali; Siegel, Barry A; Huang, Jiayi; Zan, Elcin et al. · Int J Radiat Oncol Biol Phys · 2026

prospective_cohort · Level II

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Abstract

Differentiating recurrent brain metastases (BM) from treatment-related changes after radiation therapy remains challenging. PURSUE (NCT04410367) evaluated various lesion uptake metrics to establish image interpretation criteria to detect recurrent BM with <sup>18</sup>F-fluciclovine positron emission tomography (PET). Patients with BM were enrolled if they had a previously irradiated MRI-equivocal "reference" lesion and were planned for craniotomy. PET with <sup>18</sup>F-fluciclovine (185 MBq) was performed <42 days post-MRI and 1-21 days precraniotomy. Performance of different qualitative thresholds of lesion <sup>18</sup>F-fluciclovine uptake on static PET images (10-20 minutes postinjection) versus histopathological standard of truth was assessed by 3 blinded readers, as were semiquantitative (standardized uptake value [SUV]) and dynamic uptake measures, to establish <sup>18</sup>F-fluciclovine interpretation criteria. A separate committee reviewed all data to establish interpretation criteria. Following initial review, additional blinded reads were conducted at three timepoints (10-20, 15-25, and 20-30 minutes) to explore visual-only reads (uptake ≥ parotid/pituitary as reference) and SUV ratio (SUVR)-based criteria (SUV<sub>peak(lesion-to-pituitary)</sub>). Twenty-three reference lesions from 23 subjects underwent histopathological analysis; 10 (43%) were confirmed as recurrence. At 10-20 minutes postinjection, the highest performing qualitative measure was "uptake higher than parotid" (specificity: 92%-100%; sensitivity: 40%-80% across readers). SUV<sub>max</sub> was a high-performing metric on receiver operating characteristic analysis (area under the curve: 0.87, sensitivity: 80%, specificity: 85% for SUV<sub>max</sub> threshold = 4.8). Dynamic measures provided no further diagnostic value. Additional reads showed visual-only interpretation was optimal at 15 to 25 minutes (sensitivity: 60%-90%; specificity: 77%-100%). SUVR-based interpretation using a threshold of 1.1 provided 70% to 80% sensitivity and 85% specificity. PURSUE established effective, histopathologically verified <sup>18</sup>F-fluciclovine interpretation criteria for diagnosing recurrent BM after radiation therapy that will help evaluate <sup>18</sup>F-fluciclovine PET in future studies.