Similar T/N ratio between 18F-FBPA diagnostic and BPA therapeutic dosages for boron neutron capture therapy in orthotropic tongue cancer model

Abstract

Objective: The tumor-to-normal tissue (T/N) boron ratio is determined in a patient prior to boron neutron capture therapy (BNCT) using 4-borono-2-¹⁸F-fluoro-L-phenylalanine (¹⁸F-FBPA) positron emission tomography (PET). The T/N ratio is used as a reference parameter to calculate BNCT dose and to evaluate treatment effects. The boronophenylalanine (BPA) dosage for BNCT treatment is higher than the ¹⁸F-FBPA dosage for PET diagnosis. Therefore, we aimed to determine whether the T/N ratios between diagnosis and treatment were correlated.

Methods: In this study, SAS tongue cancer cells were used to develop an orthotopic nude mouse model. Micro-PET was performed after the mice were injected a dose of 3.7 ± 0.74 MBq of ¹⁸F-FBPA via the tail vein. The ¹⁸F radioactivity in the tumor, muscle, and heart blood pool was calculated using AMIND software. Organs and blood were collected for boron concentration analysis using inductively coupled plasma-atomic emission spectroscopy after the mice were injected with 400 mg/kg BPA at 15, 30, 45, and 60 min.

Results: Pharmacokinetics of the tumor and muscle from 45 to 60 min after ¹⁸F-FBPA and BPA injections were slightly increased, whereas that of blood was slightly decreased. Median T/N ratios at 60 min after ¹⁸F-FBPA and BPA injections were 3.5 and 3.43, respectively. Median value of the T/N ratio between them was 3.49 at 60 min. The T/N ratio at 60 min after ¹⁸F-FBPA injection was similar to that after BPA injection. However, median tumor-to-blood (T/B) boron ratios of ¹⁸F-FBPA and BPA at 60 min were 1.63 and 3.35, respectively. Median value between them was 1.83 at 60 min.

Conclusions: In this study, the T/B ratios demonstrate the spread of a distribution between ¹⁸F-FBPA and BPA injections. At 60 min, the T/N ratio of the ¹⁸F-FBPA injection was similar to that of the BPA injection. Boron concentration in normal tissue was almost equal to that in blood. Therefore, the representative T/N ratio could be obtained at 60 min after ¹⁸F-FBPA injection, and it was used as a reference parameter for calculating accurate radiation dose.

Keywords: 18F-FBPA; BNCT; BPA; Pharmacokinetics; T/B ratio; T/N ratio.