Suppression of tumor growth in a rabbit hepatic cancer model by boron neutron capture therapy with liposomal boron delivery systems

Abstract

Background/Aim: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between 10B and thermal neutrons. The accumulation of 10B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation. In the present study, we examined the effects of BNCT after intra-arterial infusion of 10B-borono-dodecaborate (10BSH) by liposomal BDS in rabbit hepatic cancer models. Materials and Methods: We prepared 10BSH-entrapped transferrinconjugated polyethylene glycol liposomes constructed with distearoyl-boron lipid (TF-PEG-DSBL), and performed thermal neutron irradiation at the Kyoto University Institute for Integrated Radiation and Nuclear Science after intraarterial infusion into rabbit VX-2 hepatic tumors. Results: Concentrations of 10B in VX-2 tumors on delivery with TFPEG- DSBL liposomes reached 25 ppm on day 3 after the injection. Tumor growth was suppressed by thermal neutron irradiation after intra-arterial injection of this 10BSHcontaining liposomal BDS, without damage to normal cells. Conclusion: The present results demonstrate the applicability of 10B-containing TF-PEG-DSBL liposomes as a novel intraarterial boron carrier in BNCT for cancer.