Hironobu Yanagie1,2,3, Novriana Dewi1,3, Syushi Higashi4, Ichiro Ikushima5, Koji Seguchi4, Ryoji Mizumachi6, Yuji Murata6, Yasuyuki Morishita7, Atsuko Shinohara8, Shoji Mikado9, Nakahiro Yasuda10, Mitsuteru Fujihara11, Yuriko Sakurai1,3, Kikue Mouri1,3, Masashi Yanagawa12, Tomoya Iizuka13, Minoru Suzuki14, Yoshinori Sakurai14, Shin-Ichiro Masunaga14, Hiroki Tanaka14, Takehisa Matsukawa15, Kazuhito Yokoyama15, Takashi Fujino16, Koichi Ogura9, Yasumasa Nonaka1, Hirotaka Sugiyama1, Tetsuya Kajiyama1, Sho Yui1, Ryohei Nishimura13, Koji Ono14, Sinichi Takamoto17, Jun Nakajima3,18, Minoru Ono3,19, Masazumi Eriguchi1,20, Kenichiro Hasumi21, Hiroyuki Takahashi2,3. 1. 1 Department of Innovative Cancer Therapeutics: Alpha Particle and Immunotherapeutics, Meiji Pharmaceutical University, Tokyo, Japan. 2. 2 Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan. 3. 3 Cooperative Unit of Medicine and Engineering, The University of Tokyo Hospital, Tokyo, Japan. 4. 4 Department of Surgery, Kojinkai Medical City East Hospital, Miyazaki, Japan. 5. 5 Department of Radiology, Miyakonojyo Metropolitan Hospital, Miyazaki, Japan. 6. 6 Department of Pharmacology, Kumamoto Institute Branch, LSI Medience Co. Ltd, Kumamoto, Japan. 7. 7 Department of Human and Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 8. 8 Department of Humanities, The Graduate School of Seisen University, Tokyo, Japan. 9. 9 Department of Physics, College of Industrial Technology, Nihon University, Chiba, Japan. 10. 10 Research Institute of Nuclear Engineering, University of Fukui, Fukui, Japan. 11. 11 SPG Technology Co. Ltd, Miyazaki, Japan. 12. 12 Veterinary Medical Center, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan. 13. 13 Department of Veterinary Surgery, The University of Tokyo Veterinary Hospital, Tokyo, Japan. 14. 14 Research Reactor Institute, Kyoto University, Osaka, Japan. 15. 15 Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine, Tokyo, Japan. 16. 16 Department of Pathological Diagnosis, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. 17. 17 Department of Cardiac Surgery, Mitsui Memorial Hospital, Tokyo, Japan. 18. 18 Department of Pulmonary Surgery, The University of Tokyo Hospital, Tokyo, Japan. 19. 19 Department of Cardiac Surgery, The University of Tokyo Hospital, Tokyo, Japan. 20. 20 Department of Surgery, Shin-Yamanote Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan. 21. 21 Hasumi International Research Foundation, Tokyo, Japan.
Abstract
OBJECTIVE: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. METHODS: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm-2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. RESULTS: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. CONCLUSION: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.
OBJECTIVE:Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. METHODS: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm-2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. RESULTS: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. CONCLUSION:Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.
Authors: Y Katagiri; K Mabuchi; T Itakura; K Naora; K Iwamoto; Y Nozu; S Hirai; N Ikeda; T Kawai Journal: Cancer Chemother Pharmacol Date: 1989 Impact factor: 3.333
Authors: T Kanematsu; T Furuta; K Takenaka; T Matsumata; Y Yoshida; T Nishizaki; K Hasuo; K Sugimachi Journal: Hepatology Date: 1989-07 Impact factor: 17.425
Authors: H Yanagië; T Tomita; H Kobayashi; Y Fujii; T Takahashi; K Hasumi; H Nariuchi; M Sekiguchi Journal: Br J Cancer Date: 1991-04 Impact factor: 7.640