[F]-Fluciclovine PET Discrimination of Recurrent Intracranial Metastatic Disease from Radiation Necrosis

Background: Stereotactic radiosurgery (SRS) is often the primary treatment modality for patients with intracranial metastatic disease. Despite advances in magnetic resonance imaging, including use of perfusion and diffusion sequences and molecular imaging, distinguishing radiation necrosis from progressive tumor remains a diagnostic and clinical challenge. We investigated the sensitivity and specificity of F-fluciclovine PET to accurately distinguish radiation necrosis from recurrent intracranial metastatic disease in patients who had previously undergone SRS.

Methods: Fluciclovine PET imaging was performed in 8 patients with a total of 15 lesions that had previously undergone SRS and had subsequent MRI and clinical features suspicious for recurrent disease. The SUVmax of each lesion and the contralateral normal brain parenchyma were summated and evaluated at four different time points (5 min, 10 min, 30 min, and 55 min). Lesions were characterized as either recurrent disease (11 of 15 lesions) or radiation necrosis (4 of 15 lesions) and confirmed with histopathological correlation (7 lesions) or through serial MRI studies (8 lesions).

Results: Time activity curve analysis found statistically greater radiotracer accumulation for all lesions, including radiation necrosis, when compared to contralateral normal brain. While the mean and median SUV for recurrent disease were statistically greater than those of radiation necrosis at all time points, the difference was more significant at the earlier time points (p = 0.004 at 5 min-0.025 at 55 min). Using a SUV threshold of ≥ 1.3, fluciclovine PET demonstrated a 100% accuracy in distinguishing recurrent disease from radiation necrosis up to 30 min after injection and an accuracy of 87% (sensitivity = 0.91, specificity = 0.75) at the last time point of 55 min. However, tumor-to-background ratios (TBR) were not significantly different between recurrent disease and radiation necrosis at any time point due to variable levels of fluciclovine uptake in the background brain parenchyma.

Conclusions: Fluciclovine PET may play an important role in distinguishing active intracranial metastatic lesions from radiation necrosis in patients previously treated with SRS but needs to be validated in larger studies.