Pharmacokinetic analysis and uptake of ¹⁸f-fbpa-fr after ultrasound-induced blood-brain barrier disruption for potential enhancement of boron delivery for neutron capture therapy

Boronophenylalanine has been applied in clinical boron neutron capture therapy for the treatment of high-grade gliomas. The purpose of this study was to evaluate the pharmacokinetics of 4-borono- 2-¹⁸F-fluoro-L- phenylalanine-fructose (¹⁸F-FBPA-Fr) in F98 glioma- bearing Fischer 344 rats by means of intravenous injection of ¹⁸F-FBPA-Fr both with and without blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). Methods: Dynamic PET imaging of ¹⁸F-FBPA-Fr was performed on the ninth day after tumor implantation. Blood samples were collected to obtain an arterial input function for tracer kinetic modeling. Ten animals were scanned for approximately 3 h to estimate the uptake of ¹⁸F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model. Results: The accumulation of ¹⁸F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of ¹⁸F-FBPA-Fr with BBB-D. ¹⁸F-FBPA-Fr administration after sonication showed that the tumor-to-contralateral brain ratio for the sonicated tumors (3.5) was approximately 1.75-fold higher than that for the control tumors (2.0). Furthermore, the K1/k2 pharmacokinetic ratio after intravenous injection of ¹⁸F-FBPA-Fr with BBB-D was significantly higher than that after intravenous injection without BBB-D. Conclusion: This study demonstrated that radioactivity in tumors and the tumor-to-normal brain ratio after intravenous injection of ¹⁸F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K₁/k₂ ratio may be useful for indicating the degree of BBB-D induced by FUS. Further studies are needed to determine whether FUS may be useful for enhancing the delivery of boronophenylalanine in patients with high-grade gliomas.