The Effects of Boron Neutron Capture Therapy on Liver Tumors and Normal Hepatocytes in Mice

Abstract

To explore the feasibility of employing boron neutron capture therapy (BNCT) to treat liver tumors, the effects of BNCT were investigated by using liver tumor models and normal hepatocytes in mice. Liver tumor models in C3H mice were developed by intrasplenic injection of SCCVII tumor cells. After borocaptate sodium (BSH) and boronophenylalanine (BPA) administration, 10 B concentrations were measured in tumors and liver and the liver was irradiated with thermal neutrons. The effects of BNCT on the tumor and normal hepatocytes were studied by using colony formation assay and micronucleus assay, respectively. To compare the effects of BSH-BNCT and BPA-BNCT, the compound biological effectiveness (CBE) factor was determined. The CBE factors for BSH on the tumor were 4.22 and 2.29 using D 10 and D 0 as endpoints, respectively. Those for BPA were 9.94 and 5.64. In the case of hepatocytes, the CBE factors for BSH and BPA were 0.94 and 4.25, respectively. Tumor-to-liver ratios of boron concentration following BSH and BPA administration were 0.3 and 2.8, respectively. Considering the accumulation ratios of 10 B, the therapeutic gain factors for BSH and BPA were 0.7-1.3 and 3.8-6.6, respectively. Therefore, it may be feasible to treat liver tumors with BPA-BNCT. Key words: BNCT -BSH -BPA -Liver tumorsVarious therapeutic options have been examined for the treatment of unresectable primary and secondary malignant tumors in the liver. These include percutaneous ethanol injection, intraarterial drug infusion, embolization, intraarterial chemoembolization and radiotherapy. However, the results of these treatments have not been satisfactory. In many cases there are multiple tumors, and the liver cannot tolerate large treatment volumes, especially in radiotherapy. Boron neutron capture therapy (BNCT) which combines an administration of a tumor-seeking boron compound with thermal neutron irradiation might be an effective treatment for malignant hepatic tumors for the following reasons. In the boron neutron capture reaction, 10 B absorbs a thermal neutron and releases two high linear energy transfer (LET) particles, an α particle and a 7 Li nucleus. These particles have path lengths of 9 and 4 µm, respectively, depositing all their energy within a range of about one cell diameter from the capture reaction site. Accordingly these high-LET particles have large relative biological effectiveness (RBE), and effective cell killing can be expected in malignant tumors, which are resistant to conventional radiotherapy using photons or electrons. The path lengths of these particles are so short that if tumor cells accumulate the boron compound selectively, only tumor cells can be killed.A major limitation in the application of BNCT using thermal neutrons is the tumor depth. Deep-seated tumors, such as hepatic tumors, are difficult to treat because of the poor penetration of thermal neutrons, which have energies <0.5 eV and a 15-16 mm half-value layer in water. Epithermal beams, with energies 0.5 eV to 10 keV, have better penetration in tiss...

First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

“…In addition, RBE factors vary depending on the gamma and neutron spectra as a function of depth in tissue and dose levels, thus being different for each BNCT facility (23). Despite all the variables considered, the values obtained in this work are in the same range of those obtained by other authors in other tumor tissues and reactors (24,25). Therefore, it is not surprising that RBE values for micronuclei induction are much higher than for cell inactivation when the values found elsewhere are taken into account, considering, though, that the cell line analyzed in this work is of tumoral origin and that RBE values depend strongly on the cell type.…”

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

“…The average of the thermal neutron flux was 6.08 × 10 8 (n/cm 2 /s) and the thermal neutron fluence became 2.19 × 10 12 n/cm 2 for 60 min irradiation. The equivalent dose was calculated using the equations below …”

Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors

“…The 10 B concentrations in the tumor and the liver assumed in the present study were 197.3 and 15.3 ppm, respectively; the levels were obtained from experimental studies in animals (8). The RBE or CBE values, which were reported previously, including ours, were used in the present study (7,13,14). Table 1 summarizes the parameters used in the present study.…”

“…We have investigated the possibility of the application of BNCT to malignant liver tumors (7). Using a rat liver tumor model, we have successfully selectively accumulated high 10 B concentrations in experimental liver tumors by the intra-arterial administration of borocaptate sodium (BSH)/ lipiodol emulsion.…”