Current progress and future prospects of the VITA based neutron source

At the BINP, a pilot accelerator based epithermal neutron source is now in use. Most recent investigations on the facility are related with studying the dark current, X-ray radiation measuring, optimization of H⁻-beam injection and new gas stripping target calibrating. The results of these studies, ways of providing stability to the accelerator are presented and discussed, as well as the ways of creating the therapeutic beam and strategies of applying the facility for clinical use.     

Experimental verification of beam characteristics for cyclotron-based epithermal neutron source (C-BENS)

A cyclotron-based epithermal neutron source has been developed for boron neutron capture therapy. This system consists of a cyclotron accelerator producing 1.1-mA proton beams with an energy of 30 MeV, a beam transport system coupled with a beryllium neutron production target, and a beam-shaping assembly (BSA) with a neutron collimator. In our previous work, the BSA was optimized to obtain sufficient epithermal neutron fluxes of using a Monte Carlo simulation code. In order to validate the simulation results, irradiation tests using multi-foil activation at the surface of a gamma-ray shield located behind the collimator and water phantom experiments using a collimated epithermal neutron beam were performed. It was confirmed experimentally that the intensity of the epithermal neutrons was 1.2×10⁹ cm⁻² s⁻¹.     

Evaluation of thermal neutron irradiation field using a cyclotron-based neutron source for alpha autoradiography

It is important to measure the microdistribution of ¹⁰B in a cell to predict the cell-killing effect of new boron compounds in the field of boron neutron capture therapy. Alpha autoradiography has generally been used to detect the microdistribution of ¹⁰B in a cell. Although it has been performed using a reactor-based neutron source, the realization of an accelerator-based thermal neutron irradiation field is anticipated because of its easy installation at any location and stable operation. Therefore, we propose a method using a cyclotron-based epithermal neutron source in combination with a water phantom to produce a thermal neutron irradiation field for alpha autoradiography. This system can supply a uniform thermal neutron field with an intensity of 1.7×10⁹ (cm⁻² s⁻¹) and an area of 40 mm in diameter. In this paper, we give an overview of our proposed system and describe a demonstration test using a mouse liver sample injected with 500 mg/kg of boronophenyl-alanine.     

硼中子俘获治疗的加速器中子源7Li(p,n)7Be的中子特性研究

目的 通过研究质子加速器 ⁷Li(p,n)⁷Be 反应的中子特性,为研究和制作适用于硼中子俘获治疗(BNCT)的加速器中子源提供基础数据。方法 加速质子使其轰击Li靶后产生中子;通过金属箔活化法,测量中子与In箔发生阈值反应后放出的γ射线;然后计算出In箔的放射性活度、加速器反应后放出中子的注量和反应的微分截面。结果 质子加速轰击Li靶后,在不同方向产生不同能量和注量的中子。加速器电压分别为3.0、2.8和2.6 MV,出射中子与入射质子束的方向一致时, ⁷Li(p,n)⁷Be 反应的微分截面约为50 mb/mr;夹角为60°时,反应的微分截面减小到30 mb/mr左右。由于部分中子与其他金属原子等发生弹性散射而射向后方,提高了这一范围内In箔的比放射性活度,影响了其微分截面的准确性。结论 用金属箔活化法测定中子简便易行,可同时测得多个方向的中子分布,但需对中子与其他金属弹性散射产生的影响进行进一步的研究; ⁷Li(p,n)⁷Be 反应后发射出的中子经慢化后,能得到适于BNCT治疗的热中子和超热中子;若作为BNCT的中子源,加速器的质子束流需达到10 mA。     

Optimization of the target of an accelerator-driven neutron source through Monte Carlo numerical simulation of neutron and gamma transport by the PRIZMA code

At Budker Institute of Nuclear Physics, epithermal neutron source for neutron-capture therapy was built and neutron generation was realized. Source is based on tandem accelerator and uses near-threshold neutron generation from the reaction ⁷Li(p,n)⁷Be. The paper describes target optimization through the numerical simulation of proton, neutron and gamma transport by Monte Carlo method (PRIZMA code). It is shown that the near-threshold mode attractive due low activation provides high efficiency of the dose and acceptable therapeutic ratio and advantage depth.     

硼中子俘获治疗(BNCT)设备中子束流质量控制检测项分析

目的通过对医院中子照射器(IHNI)的超热中子束流辐射特性参数和剂量学特性参数的检测, 为建立硼中子俘获治疗(BNCT)设备中子束流的质量控制检测方法提供参考。方法通过对比各项检测结果的不确定度与欧洲联合研究中心(EC-JRC)推荐的偏差值, 分析评估相应检测方法的可行性。结果超热中子注量率的不确定度为2.7%;热中子与超热中子注量率比值的不确定度为3.1%;快中子空气比释动能率与超热中子注量率比值的不确定度为9.3%;γ空气比释动能率与超热中子注量率比值的不确定度为8.7%;中子注量率空间分布的不确定度为2.7%;模体内热中子注量率的不确定度为1.8%;模体内中子和γ射线剂量率的不确定度分别为17.1%和4.0%。结论模体内中子剂量率测量结果不确定度高, 需要进一步研究该项检测方法来提高检测结果的准确度;其余检测项测量结果不确定度低, 检测结果准确度预期能满足欧洲联合研究中心的推荐允许偏差值, 检测方法可行。     

硼中子俘获疗法促人黑色素瘤细胞凋亡

目的 研究硼中子俘获疗法(BNCT)体外杀伤人黑色素瘤细胞的效应及机制.方法 首先检测黑色素瘤细胞A375吸收含硼化合物二羟基苯丙氨酸硼(BPA)的情况,然后采用医院中子照射器(IHNI-1)对含硼(10B)细胞进行照射.克隆存活实验检测细胞的放射敏感性,MTT法检测细胞增殖率,流式细胞术检测凋亡,Western blot检测胞质内细胞色素C表达和caspase-9的激活.结果 BPA孵育24 h,A375细胞10B浓度为(2.884±0.148)μg/107个细胞,达到了BNCT杀伤细胞的要求.富含10B的细胞经中子照射2.1 min后存活分数降低为对照组的58％(t=2.964,P＜0.05),细胞经中子照射后24 h增殖率下降为对照组的83％(t=3.286,P＜0.05),BNCT组细胞凋亡率达(55.2±7.9)％,明显高于对照组(t =9.754,P＜0.05),胞质内细胞色素C水平上升且caspase-9激活程度增加(t=7.625、8.307,P＜0.05).结论 BNCT能够杀伤黑色素瘤细胞,其机制可能通过线粒体途径诱导细胞凋亡.     

用于硼中子俘获治疗的超热中子束理论设计

目的 设计用于硼中子俘获治疗(BNCT)的超热中子束理论方案。方法 基于清华大学试验核反应堆,以其1号孔道为材料布放孔道,设计了由慢化材料、热中子吸收材料、γ屏蔽材料组成,但材料布放位置具有差异的5种理论方案;利用蒙特卡罗(MC)模拟方法,分别计算5种方案束出口处的中子注量率、剂量率及γ剂量率值,通过与BNCT技术指标对比,从5种方案中选择一种合适的方案。结果 得到了一个符合BNCT各项技术指标的超热中子束理论方案,其慢化材料厚度为53.5 cm、热中子吸收材料厚度为2 mm、γ屏蔽材料厚度为9 cm。结论 本研究给出的超热中子束理论方案为基于反应堆实现BNCT提供一定的理论参考。     

The determination of uranium in food samples by Compton suppression epithermal neutron activation analysis

Eight foods common to the Nigerian diet were analyzed for trace amounts of uranium using epithermal neutron activation analysis. Food sample sizes of roughly one-half gram, irradiated for 10 min, with a 15 min decay time and counting time for 10 min yielded detection limits between 0.02 and 0.04 Bq/kg. Dried milk, chicken pasta, spaghetti and biscuits had less than detectable amounts of uranium, while sorghum, wheat and brown beans contained 0.73, 0.23 and 0.16 Bq/kg, respectively.     

肿瘤硼中子俘获治疗的理论基础与近期研究进展

硼中子俘获治疗(BNCT)是一种新型肿瘤精准治疗方法 ,通过肿瘤细胞内的10B俘获热中子发生核裂变反应产生a粒子和反冲7Li核选择性地杀死肿瘤细胞.将足量的10B选择性递送到肿瘤细胞内部是BNCT成功的关键.本文简要介绍了BNCT治疗肿瘤的理论基础,综述了BNCT所用的中子源和硼递送剂的近期研究进展,简述了BNCT临床...     

硼中子俘获治疗剂量验证方法进展

硼中子俘获治疗(BNCT)利用中子与肿瘤细胞中富集的硼发生特异性俘获反应, 可以定向杀死癌细胞。为了验证中子放疗计划的准确性, 保障患者的治疗效果, 需要在治疗前进行剂量验证, 即对比分析实验照射剂量与计划剂量。目前, BNCT剂量测量方法主要包括电离室法、热释光法、活化法等点剂量测量方法, 基于胶片的二维剂量测量方法, 以及基于凝胶剂量仪的三维剂量测量方法。本文总结了国际上BNCT剂量验证方法的进展, 讨论了这些方法的发展前景。     

硼中子俘获疗法诱导SHG44胶质瘤细胞凋亡

目的 探讨硼中子俘获疗法(BNCT)是否抑制人脑胶质瘤细胞SHG44增殖及其作用机制。方法 BNCT作用后,应用四甲基偶氮唑蓝比色法检测SHG44细胞的增殖抑制,采用光镜、电镜、荧光显微镜观察细胞的形态学变化。应用流式细胞仪检测SHG44细胞的凋亡率,以Western blot检测细胞表达Bcl-2、Bax蛋白的变化。结果 BNCT对SHG44细胞的增殖抑制作用呈剂量依赖性。BNCT 4和8 Gy后48 h流式细胞仪检测凋亡率分别为63.2%和88.3%。BNCT作用后,Bax蛋白表达增高,Bcl-2蛋白表达下降。结论 BNCT对胶质瘤细胞SHG44具有明显的增殖抑制及诱导凋亡作用,并使Bax蛋白表达上调、Bcl-2蛋白表达下调。     

硼中子俘获治疗头颈部肿瘤临床试验进展

硼中子俘获治疗（boron neutron capture therapy,BNCT）是结合靶向治疗和重离子治疗的先进二元放疗技术。其原理是利用含有¹⁰B同位素的硼药在肿瘤细胞中靶向聚集,随后中子束流外部照射肿瘤部位,发生¹⁰B（n,α）⁷Li核反应,释放出杀伤范围为一个细胞大小（5~9 μm）的高传能线密度α粒子和⁷Li粒子杀死肿瘤细胞。BNCT具有精准的肿瘤靶向性,对正常组织损伤小,分割次数（1~3次）少于传统放疗（30次）等优点。BNCT使用的中子由反应堆或加速器产生,临床使用的硼药包括BPA和BSH两种。本文介绍国内外开展的头颈部肿瘤BNCT临床试验及取得的重要进展。BNCT对于头颈部肿瘤治疗具有良好疗效。随着加速器中子源的推广应用和新型硼药的研发,BNCT将会在临床放射治疗领域发挥更大的作用。     

Low dose of gamma irradiation enhanced boronophenylalanine uptake in head and neck carcinoma cells for boron neutron capture therapy

This study attempted to increase the boron uptake of human head and neck carcinoma SAS cells for BNCT by using a gamma dose of 0.1 Gy for combined treatment. Intracellular boron concentrations in 25 μg B/mL medium of BPA treated and BPA combined gamma-irradiation treated SAS cells were 73.8±1.73 and 95.15±1.36 ppm, respectively. After neutron irradiation, the G2/M-phase cell populations of untreated, BPA treated and BPA combined gamma-irradiation treated SAS cells were 19.31±1.71%, 52.47±2.25% and 59.19±2.63%, respectively. Experimental results indicate that the low dose gamma radiation with combination BPA treatment has the highest killing rate after neutron irradiation. Capable of significantly increasing the G2/M arrest after neutron irradiation, the combined treatment of a low dose of gamma irradiation with 25 μg B/mL medium of BPA also provided a higher killing effect for BNCT.     

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: A boron neutron capture therapy study

Abstract

Purpose: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined.

Materials and methods: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from ¹⁰B thermal neutron capture.

Results: BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/10⁹ cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10¹¹ n/cm² thermal neutron fluence yielded a 20–25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and ⁷Li nuclei that deposit energy in densely ionizing radiation tracks.

Conclusion: Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and ⁷Li nuclei generated from ¹⁰B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.     

Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: A case report

Boron neutron capture therapy (BNCT) has been reported to be effective in the patients with glioblastoma multiforme (GBM). Median survival time (MST) of GBM patients treated with BNCT is approximately two years. GBM patients surviving 2 or 3 years are considered long-term survivors. In general, most recurrences are local and dissemination is rare. We report an unusual patient with three recurrences; the first and the second recurrences were local, and the third recurrence was dissemination nine years after BNCT.     

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a 10BSH-containing WOW emulsion

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a ¹⁰BSH-containing water-in-oil-in-water emulsion (¹⁰BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that ¹⁰BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC.     

Boronated unnatural cyclic amino acids as potential delivery agents for neutron capture therapy

Boron delivery characteristics of cis and trans isomers of a boronated unnatural amino acid, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) were tested in the B16 mouse model for human melanoma. Both ABCPC isomers delivered comparable boron to B16 melanoma tumor cells as l-p-boronophenylalanine (BPA). Secondary ion mass spectrometry (SIMS) analysis revealed the presence of boron throughout the tumor from these compounds, and a near homogeneous distribution between the nucleus and cytoplasm of B16 cells grown in vitro. These encouraging observations support further studies of these new boron carriers in BNCT.     

A phantom experiment for the evaluation of whole body exposure during BNCT using cyclotron-based epithermal neutron source (C-BENS)

At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics.In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported.