在肝癌模型中通过动脉内注射硼酸钠-哇巴因（BSH-WOW）乳剂进行中子俘获治疗时的选择性硼递送。
Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.
作者信息
Yanagie Hironobu, Dewi Novriana, Higashi Syushi, Ikushima Ichiro, Seguchi Koji, Mizumachi Ryoji, Murata Yuji, Morishita Yasuyuki, Shinohara Atsuko, Mikado Shoji, Yasuda Nakahiro, Fujihara Mitsuteru, Sakurai Yuriko, Mouri Kikue, Yanagawa Masashi, Iizuka Tomoya, Suzuki Minoru, Sakurai Yoshinori, Masunaga Shin-Ichiro, Tanaka Hiroki, Matsukawa Takehisa, Yokoyama Kazuhito, Fujino Takashi, Ogura Koichi, Nonaka Yasumasa, Sugiyama Hirotaka, Kajiyama Tetsuya, Yui Sho, Nishimura Ryohei, Ono Koji, Takamoto Sinichi, Nakajima Jun, Ono Minoru, Eriguchi Masazumi, Hasumi Kenichiro, Takahashi Hiroyuki
机构信息
1 Department of Innovative Cancer Therapeutics: Alpha Particle and Immunotherapeutics, Meiji Pharmaceutical University, Tokyo, Japan.
2 Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
出版信息
Br J Radiol. 2017 Jun;90(1074):20170004. doi: 10.1259/bjr.20170004. Epub 2017 May 25.
OBJECTIVE
Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a BSH-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 BSH-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 × 10 n cm. Morphological and pathological analyses were performed on Day 14 after neutron irradiation.
RESULTS
Biodistribution results have revealed that B 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 BSH-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 BSH-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 BSH 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.
目的
硼中子俘获疗法（BNCT）已被用于抑制各类癌症的生长。在本研究中，我们制备了包裹硼酸钠（BSH）的水包油包水（WOW）型乳剂，并评估其作为选择性硼载体在BNCT治疗肝细胞癌中的应用潜力。
方法
我们采用二次乳化技术制备了包裹BSH的WOW乳剂，然后通过在VX-2兔肝肿瘤模型上进行生物分布实验来评估其递送效果，并与碘化罂粟籽油混合常规乳剂进行比较。在京都大学研究反应堆进行中子辐照，平均热中子注量为5×10⁹n/cm²。在中子辐照后第14天进行形态学和病理学分析。
结果
生物分布结果显示，与使用碘化罂粟籽油常规乳剂相比，WOW乳剂的硼原子递送效果更佳。在用包裹BSH的WOW乳剂治疗的组中，中子辐照后未观察到腹部扩散或肺转移，而在未注射组中，肝脏、腹腔、腹膜和双侧肺叶中发现了许多肿瘤结节。
结论
从对注射包裹BSH的WOW乳剂组的形态学和病理学分析中观察到肿瘤生长抑制和癌细胞杀伤作用，表明其作为BNCT新型动脉内硼载体应用的可行性。知识进展：本研究结果表明，包裹的BSH有可能增加肝细胞癌的治疗选择范围，肝细胞癌被认为是最难治愈的肿瘤之一。
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