Hironobu Yanagie1,2,3, Masashi Yanagawa4, Yasuyuki Morishita5, Atsuko Shinohara6, Novriana Dewi7, Yasumasa Nonaka8, Yoshitaka Furuya9, Ryouji Mizumachi10, Yuuji Murata10, Hiroyuki Nakamura11, Minoru Suzuki12, Yoshinori Sakurai12, Hiroki Tanaka12, Shinichiro Masunaga12, Koji Ono13, Takumichi Sugihara7, Masayuki Nashimoto3, Haruo Yamauchi2,14, Minoru Ono2,14, Jun Nakajima2,15, Hiroyuki Takahashi16,2. 1. Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, Japan; h.yanagie@gmail.com. 2. Cooperative Unit of Medicine and Engineering, The University of Tokyo Hospital, Tokyo, Japan. 3. Research Institute of Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. 4. Veterinary Medical Center, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan. 5. Department of Human and Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 6. Graduate School of Humanities, Seisen University, Tokyo, Japan. 7. Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. 8. Department of Surgery, Keiai-kai Houyou Hospital, Hanamaki, Japan. 9. Department of Surgery, Sodegaura Satukidai Hospital, Sodegaura, Japan. 10. Department of Pharmacology, Kumamoto Institute Branch, LSI Medience Ltd. Co., Uto, Japan. 11. Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan. 12. Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka, Japan. 13. BNCT Joint Clinical Institute, Osaka Medical Pharmaceutical University, Osaka, Japan. 14. Department of Cardiovascular Surgery, The University of Tokyo Hospital, Tokyo, Japan. 15. Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan. 16. Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, Japan.
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 transferrin-conjugated 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 intra-arterial infusion into rabbit VX-2 hepatic tumors. RESULTS: Concentrations of 10B in VX-2 tumors on delivery with TF-PEG-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 10BSH-containing liposomal BDS, without damage to normal cells. CONCLUSION: The present results demonstrate the applicability of 10B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.
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 transferrin-conjugated 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 intra-arterial infusion into rabbit VX-2 hepatic tumors. RESULTS: Concentrations of 10B in VX-2 tumors on delivery with TF-PEG-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 10BSH-containing liposomal BDS, without damage to normal cells. CONCLUSION: The present results demonstrate the applicability of 10B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.