TB-6 Experimental evaluation of the therapeutic potential of boron neutron capture therapy in primary central nervous system lymphoma

Abstract

Background: High-dose methotrexate and whole brain radiation therapy (WBRT) is the recommended treatment for primary central nervous system lymphoma (PCNSL). Although the initial treatment is successful, the recurrence rate is high and the prognosis is poor. Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when non-radioactive boron-10 is irradiated with neutrons to produce α particles (10B [n, α] 7Li). In this study, we conducted a basic research to explore the possibility of BNCT as a treatment option for PCNSL. Methods: Cellular uptake of boron using human lymphoma cell-lines after exposure to boronophenylalanine (BPA) were evaluated. The cytotoxicity of lymphoma cells by photon irradiation or neutron irradiation with BPA were also evaluated. The lymphoma cells were implanted into the mouse brain and the bio-distribution of boron after administration of BPA were measured. In neutron irradiation studies, the therapeutic effect of BNCT on mouse CNSL models were evaluated in terms of survival time. Results: The boron concentration in lymphoma cells after BPA exposure was sufficiently high, and lymphoma cells showed cytotoxicity by photon irradiation, and also by BNCT. In in vivo bio-distribution study, lymphoma cells showed enough uptake of BPA with well contrasted to the brain. In the neutron irradiation experiment, the BNCT group showed a significant prolongation in their survival time compared to the control group. Conclusions: In our study, BNCT showed its effectiveness for PCNSL in a mouse brain tumor model. PCNSL is a radio-sensitive tumor with a extremely good response rate, but it also has a high recurrence rate / a high rate of adverse events, so there is no effective treatment for recurrence after treatment. Our translational study showed that BNCT is possibly have an important role against PCNSL during the therapy lines as a new treatment option for PCNSL patients.