Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of 10B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared 10BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), 10BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The 10B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that 10B entrapped WOW emulsion could be applied to novel intra-arterial boron delivery carrier for BNCT, and we show the possibility to apply BNCT to HCC. We can irradiate tumours as selectively and safety as possible, reducing the effects on neighbouring healthy tissues. - Research highlights: ► It is necessary to accumulate a sufficient quantity of 10B atoms in tumor cells for effective tumor cell destruction by BNCT. ► BSH entrapped WOW emulsion by double emulsifying method was prepared as novel intra-arterial boron delivery carrier for BNCT. ► We simulated the irradiation of epithermal neutron and calculated dose delivered to HCC patient with JCDS at JRR4 reactor.