Clinical Utility of Fluciclovine PET in BNCT for Recurrent High-grade Glioma

Boron Neutron Capture Therapy (BNCT) has gained popularity in recent years, with over 500 treatment courses performed in Taiwan since 2017. Traditionally, the tumor-to-normal tissue ratio (T/N ratio) is assessed using SUV measurements from 4-borono-2-(18) F-fluoro-phenylalanine (F-BPA) PET, allowing for precise tumor boron concentration estimation when serum boron levels are measured on the day of treatment. However, limited accessibility to F-BPA PET complicates dose calculations, and in its absence, a fixed T/N ratio of 3 is used in treatment planning. Fluciclovine PET has recently been explored as an alternative, as both fluciclovine and BPA share the L-type amino acid transporter 1 (LAT-1) transporter, although fluciclovine can also be transported via alanine-serine-cysteine transporter 2 (ASCT2). However, its accuracy in reflecting BPA distribution and its correlation with treatment response remain uncertain.

Since June 2022, fluciclovine PET has been used for brain tumor evaluation in Taiwan. By June 2024, 80 brain tumor patients underwent pre-BNCT assessment with fluciclovine PET. After excluding those who received a second treatment course, 44 patients were analyzed. The average T/N ratio in this cohort was 4.6, higher than reported averages for F-BPA PET (2.5 for head and neck tumors, 3 for brain tumors). The tumor response rate was defined as patients achieving either a complete or partial response, as evaluated by experienced neuroradiologists. Patients were categorized based on response achievement, and potential prognostic factors were compared.

The mean T/N ratio of fluciclovine PET was 4.61±1.43 (range: 2.58-8.86). Among 15 patients who underwent follow-up fluciclovine PET 3 months post-BNCT, the mean T/N ratio decreased significantly to 2.85±1.16 (range: 1.00-5.47). Treatment response assessment at 3 months post-BNCT revealed that 4 patients achieved complete response (CR), 26 had partial response (PR), 5 exhibited stable disease (SD), and 9 experienced progressive disease (PD). Responders had significantly smaller tumors compared with nonresponders (35.74 vs. 83.83 cm³, p =0.009) and received higher minimum tumor doses (18.50 vs. 12.13 GyE, p =0.033). In addition, a significant decline in T/N ratio was observed following BNCT, decreasing from 4.602±0.368 pretreatment to 2.847±0.300 at 3 months post-treatment.

Our findings suggest that while fluciclovine PET may provide an estimate of BPA uptake, it is not a reliable predictor of treatment response. However, it remains an effective tool for assessing treatment effect following BNCT. Further studies are necessary to identify key prognostic factors for selecting BNCT candidates and to determine whether fluciclovine PET can effectively predict BNCT outcomes.