Abstract
Abstract In this research, a rat model for hepatocellular carcinoma (HCC) was set up, and the boric acid (BA) and PBAD-lipiodol were used as the boron drugs. The pharmacokinetics, radiobiological effects and therapeutic efficacy of boric acid for boron neutron capture therapy (BNCT) for hepatocellular carcinoma were evaluated. The in vitro and in vivo experiments and the boron drug synthesis were included in this study. HepG2 cells and Clone 9 cells were incubated in culture media containing different concentrations of BA for the cytotoxicity test and uptake evaluation. Concerned with the cytotoxicity of BA and the cellular uptake, we decided to use 25 mg 10B/kg bw BA to treat the tumor bearing rats. BA was injected from the tail vein of rats to assess the biodistribution and pharmacokinetics, and to determine optimal time interval for neutron irradiation. Boron concentration was analyzed by the ICP-AES. The tumor bearing rats were irradiated with neutron after 30 minutes of boron drug injection and were given four level prescription doses to evaluate the radiobiological effects and therapeutic efficiency of BNCT. Ultrasound imaging was used to monitor the changes of tumor size, and doppler imaging was used for the detection of blood flow change after BNCT treatment. The tumor size and blood flow were decreased after BNCT. However, at the fourth day after BNCT treatment, rats showed some radiation damages, such as diarrhea and lymphocyte diffuse, but these damages were disappearing late. Rats were sacrificed at different intervals after BNCT, and tumor mass was controlled in the good status at the 30th days, and was disappeared at the 80th days. Because the rats were too small to obtain in an applicative shielding, the testis was fall in the beam port. Thus, the testes showed a dose-dependent atrophy after BNCT treatment. In this study, we also used hepatic artery injection to assess the PBAD-lipiodol distribution in the rat liver. The accumulation of PBAD-lipiodol in the tumor region was higher than that in normal liver tissue, but with a non-uniform distribution. We suggested that it might be a good choice to combined boric acid and PBAD-lipiodol in BNCT for hepatoma, which might be able to increase the boron concentration in tumor region. Key words：Boron neutron capture therapy (BNCT), Hepatocellular carcinoma (HCC), Boric acid (BA), PBAD-lipiodol