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.