Suitability of boron carriers for BNCT: accumulation of boron in malignant and normal liver cells after treatment with BPA, BSH and BA

Abstract

Hepatocellular carcinoma remains widely prevalent in tropical Africa and south-east Asia. At present, there are no effective treatments for hepatoma and its prognosis is extremely poor unless the tumor was diagnosed in an early stage and resected before metastasis. Therefore, boron neutron capture therapy (BNCT) may provide an alternative therapy for treatment of hepatocellular carcinoma. In this study, the intracellular concentrations of L-boronophenylalanine (BPA), sodium borocaptate (BSH) and boric acid (BA) were examined in human hepatoma HepG2 and liver Clone 9 cell cultures. With the use of 25 microgB/mL media of BPA, BSH and BA, the intracellular uptake of boron in HepG2 and Clone 9 cells was compared. The suitability of BPA, BSH and BA were further evaluated on the basis of organ-specific boron distribution in normal rat tissues. BPA, BSH and BA were administered via intraperitoneal injection into rats with corresponding boron concentrations of 7, 25, and 25mg/kg body weight, respectively. The accumulation rates of BPA, BSH and BA in HepG2 cells were higher than that of Clone 9 cells. Boron concentration in BPA, BSH and BA treated HepG2 cells were 1.8, 1.5, and 1.6-fold of Clone 9 cells at 4h, respectively. In both HepG2 and Clone 9 cells, although the concentration of boron in BPA-treated cells exceeded that in BA-treated ones, however, cells treated with BPA had similar surviving fraction as those treated with BA after neutron irradiation. The accumulation ratios of boron in liver, pancreas and kidney to boron in blood were 0.83, 4.16 and 2.47, respectively, in BPA treated rats, and 0.75, 0.35 and 2.89, respectively, in BSH treated rats at 3h after treatment. However, boron does not appear to accumulate specifically in soft tissues in BA treated rats. For in situ BNCT of hepatoma, normal organs with high boron concentration and adjacent to liver may be damaged in neutron irradiation. BPA showed high retention in pancreas and may not be a good drug for BNCT of hepatoma. BSH had higher retention in liver but low level in pancreas and spleen appears to be a better candidate BNCT drug for hepatoma. These preliminary results provide useful information on future application of BNCT for hepatoma.