Romanian experimental research on boron neutron capture therapy (BNCT) in liver tumors.

Abstract

e21111 Background: BNCT is based on the nuclear reaction following irradiation of Boron-10 (B-10) with low-energy neutrons and on the selective delivery of B-10 to tumor cells, which can lead to selective irradiation. Our objective was to develop a preclinical model for the BNCT in animals with experimental hepatoma with Romanian nuclear facilities. Methods: We use nuclear reactor TRIGA-ACPR to realize the experimental irradiation. The experimental models were RS1 hepatoma-bearing rats. We induce the RS-1 hepatoma by 2-acetylaminofluorene administration in rats' food. We injected intravenously Bor-Phenil-Alanin (BPA) solution in 5% fructose. We measure the BPA level into the tumor at 1, 3 and 6 hours after injection. The rats were irradiated 3 hours after B delivery for 1 or 2 hours. We evaluate the biologic effects of the BNCT using blood and tumor samples, which were obtained 2 hours after end of irradiation. We measured cytotoxic effects of BNCT by measuring apoptosis using flow-citometry and by measuring oxidative stress using biochemical tests (MDA and SH). We also measure apoptosis after bevacizumab administration. Results: The BPA was selectively accumulated at the tumor level, with a maximum level at 3 hours after administration. At the liver level we observed an increase of apoptosis rate both at one hour and 2 hours of irradiation (70.42% and 72.98%) compare to apoptosis rate in basal condition which was 27.8%. At the tumor level the number of apoptotic cells was unsignificant for one-hour irradiation and was 34.35% for 2 hours irradiation, compare to the initial value (11.48%). The MDA (8.64 μmoli/100 mL vs 7.18 μmoli/100 mL) and SH (253 μmoli/L vs 440 μmoli/L) levels in the tumor tissue were higher after irradiation, suggesting that the cytotoxic oxidative reactions were initiated. We also observed an increased level of apoptotic cells after 2 doses of 5 mg/kgc bevacizumab before BNCT irradiation. Conclusions: The BPA level into tumor tissue was maximum after 3 hours from the administration. The apoptotic level into the tumor was higher for a 2 hours irradiation. The association between antiangiogenic agents and BNCT deserve further research. Our experiment creates the premises for clinical research on BNCT in Romania. No significant financial relationships to disclose.