The Anti-Tumor Effect of Boron Neutron Capture Therapy in Glioblastoma Subcutaneous Xenograft Model Using the Proton Linear Accelerator-Based BNCT System in Korea

Abstract

Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells and is being actively researched and developed around the world. In Korea, development of the proton linear accelerator-based BNCT system has completed development, and its anti-cancer effect in the U-87 MG subcutaneous xenograft model has been evaluated. To evaluate the efficacy of BNCT, we measured 10B-enriched boronophenylalanine (BPA) uptake in U-87 MG, FaDu, and SAS cells and evaluated cell viability by clonogenic assays. In addition, the boron concentration in the tumor, blood, and skin on the U-87 MG xenograft model was measured, and the tumor volume was measured for 4 weeks after BNCT. In vitro, the intracellular boron concentration was highest in the order of SAS, FaDu, and U-87 MG, and cell survival fractions decreased depending on the BPA treatment concentration and neutron irradiation dose. In vivo, the tumor volume was significantly decreased in the BNCT group compared to the control group. This study confirmed the anti-cancer effect of BNCT in the U-87 MG subcutaneous xenograft model. It is expected that the proton linear accelerator-based BNCT system developed in Korea will be a new option for radiation therapy for cancer treatment.

Advances of LINAC-based boron neutron capture therapy in Korea

“…The BNCT therapeutic efficacies in vitro and in vivo experiments have been studied at the DM A-BNCT facility. The results were published very recently [50]. For evaluation of the efficacy of BNCT, U-87 MG cells were selected as representative brain cancer, and FaDu and SAS cell lines were chosen for head and neck cancers for in vitro study.…”

“…Thus, for the U-87 MG, FaDu, and SAS BNCT groups, the results showed that the survival fractions were decreased proportionally depending on BPA treatment concentration and neutron irradiation dose. Figure 22 shows the results of in vitro test for the FaDu cell, which is selected from the reference [50].…”

“…Groups 4 and 5 with skin doses of 5 and 6 Gy-Eq each had a significant decrease in tumor volume from the 6th and 8th days, respectively. Figure 23 shows the in vivo test results from reference [50].…”

“…The original seraMC engine has been modified Fig. 22 Cell viability estimation after BNCT treatment for FaDu cells showing a very high therapeutic efficacy [50] and upgraded to on a modern parallel computing server. The TPS then calculates the total dose which is converted to "monitor units (MU), " and termination limits are set to end the neutron irradiation after the prescribed dose has been delivered.…”

“…a Tumor growth as a function of time after the finish of neutron irradiation. b The visual tumor appearance at 4 weeks after the neutron irradiation[50]…”