Unexpected [18F]-fluciclovine hyperuptake in radiation necrosis after proton therapy: illustrative case.

background[18F]-Fluciclovine PET is increasingly used for visualizing malignant gliomas and delineating tumor infiltration. More recently, its utility has been reported in differentiating tumor recurrence from radiation necrosis (RN). However, the behavior of [18F]-fluciclovine PET in newly identified intracranial contrast-enhancing lesions, particularly at initial presentation, remains unclear. OBSERVATIONS: A 57-year-old man developed a new ring-enhancing lesion in the left frontal lobe 4.5 years after proton therapy for ethmoid sinus carcinoma. MRI demonstrated progressive enlargement of the lesion over 4 months. [18F]-Fluciclovine PET showed moderate uptake (maximum standardized uptake value [SUV ] 2.96) with a markedly elevated tumor-to-background ratio (TBR 22.77), raising concern for a high-grade glioma. Resection was performed; however, histopathological and molecular analyses confirmed RN. LESSONS: This rare case highlights an important diagnostic pitfall in which [18F]-fluciclovine PET demonstrates markedly elevated TBR despite only moderate SUV in RN. Discordant findings between SUV and TBR should be interpreted cautiously, as they may not always indicate active tumor. Careful integration of clinical course, longitudinal imaging findings, and treatment history is important for appropriate clinical decision-making. https://thejns.org/doi/10.3171/CASE26222.