Yanagie Hironobu, Kumada Hiroaki, Nakamura Takemi, Higashi Syushi, Ikushima Ichiro, Morishita Yasuyuki, Shinohara Atsuko, Fijihara Mitsuteru, Suzuki Minoru, Sakurai Yoshinori, Sugiyama Hirotaka, Kajiyama Tetsuya, Nishimura Ryohei, Ono Koji, Nakajima Jun, Ono Minoru, Eriguchi Masazumi, Takahashi Hiroyuki
Department of Nuclear Engineering & Management, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Appl Radiat Isot. 2011 Dec;69(12):1854-7. doi: 10.1016/j.apradiso.2011.04.022. Epub 2011 May 20.
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 (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B 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 (10)BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), (10)BSH 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.
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.
The (10)B 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 (10)B 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.
肝细胞癌（HCC）是最难通过手术、化疗或其他联合疗法治愈的癌症之一。在HCC的治疗中，由于肝硬化或多发性肝内肿瘤等并发症，只有30%的患者能够接受手术。硼中子俘获疗法（BNCT）中肿瘤细胞的破坏是由于（10）B原子与热中子之间的核反应，因此有必要在肿瘤细胞中积累足够数量的（10）B原子，以便通过BNCT有效破坏肿瘤细胞。水包油包水（WOW）乳液已在临床上用作动脉内注射抗癌药物的载体。在本研究中，我们使用碘化罂粟籽油（IPSO）、（10）BSH和表面活性剂，通过双重乳化技术制备了包裹（10）BSH的WOW乳液，用于选择性肝动脉内注入HCC，并进行了辐照模拟，以计算给予患者的剂量。
通过适当的肝动脉对VX-2兔肝肿瘤模型进行动脉内注射WOW乳液。我们模拟了超热中子的辐照，并使用日本原子能研究所JRR4反应堆的JAEA计算剂量测定系统（JCDS），根据一名HCC患者的CT扫描结果，计算了给予组织的剂量。
通过WOW乳液给药获得的VX-2肿瘤中的（10）B浓度优于传统IPSO混合乳液。根据兔模型，肿瘤、正常肝组织和血液中的硼浓度（ppm）分别为61.7、4.3和0.1。模拟结果表明，正常肝脏的生物加权剂量限制在4.9 Gy-Eq（CBE；肝肿瘤：2.5，正常肝脏：0.94）；在40分钟的辐照中，肿瘤加权剂量的最大值、最小值和平均值分别为43.1、7.3和21.8 Gy-Eq。在本研究中，我们表明包裹（10）B的WOW乳液可作为BNCT新型动脉内硼递送载体应用，并且我们展示了将BNCT应用于HCC的可能性。我们可以尽可能选择性和安全地辐照肿瘤，减少对邻近健康组织的影响。
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