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.     

硼中子俘获治疗技术的研究现状

对硼中子俘获治疗技术的原理、硼中子俘获治疗系统需要研究的相关内容及研究现状作了主要介绍；对加速器或反应堆产生超热中子束的方法及与硼中子俘获治疗相关的硼化合物作了较详细的讨论。     

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。     

硼中子俘获治疗技术的研究现状

对硼中子俘获治疗技术的原理、硼中子俘获治疗系统需要研究的相关内容及研究现状作了主要介绍;对加速器或反应堆产生超热中子束的方法及与硼中子俘获治疗相关的硼化合物作了较详细的讨论。     

硼中子俘获治疗的辐射场特点与剂量估算

BNCT（硼中子俘获治疗）基于这样一种思想：^10B的载体化合物会优先选择癌细胞作为靶而后与热中子反应，进而产生高能、短射程裂变产物α粒子和Li粒子。它是一种双重的靶向治疗方法。BNCT的治疗效果依赖于两个主要因素：源于^10B（n,α）^7Li核反应的高LET（传能线密度）粒子的生物效应和在靶细胞及其特异区域内的硼沉积。本总结和探讨了BNCT的发展概况、辐射场的特点以及吸收剂量的计算方法。     

硼中子俘获治疗的辐射场特点与剂量估算

BNCT(硼中子俘获治疗)基于这样一种思想:10B的载体化合物会优先选择癌细胞作为靶而后与热中子反应,进而产生高能、短射程裂变产物α粒子和Li粒子。它是一种双重的靶向治疗方法。BNCT的治疗效果依赖于两个主要因素:源于10B(n,α)7Li核反应的高LET(传能线密度)粒子的生物效应和在靶细胞及其特异区域内的硼沉积。本文总结和探讨了BNCT的发展概况、辐射场的特点以及吸收剂量的计算方法。     

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。     

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...     

硼中子俘获治疗的生物学机制及临床研究进展

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种新型且高度精准的肿瘤放疗手段。BNCT可依赖高效靶向的含硼药物,在细胞级别同时实现对肿瘤细胞的精准打击和对正常细胞的精准防护。含硼药物研发正在深入进行,新型高效的制剂层出不穷,这为充分发挥BNCT优势和疗效带来新的曙光。由于BNCT过程中产生复合射线,其对肿瘤细胞的杀伤机制较为复杂,相关研究仍相对匮乏,具体分子机制有待阐明和完善。世界范围内,BNCT已用于恶性脑瘤、头颈部肿瘤、恶性黑色素瘤等临床治疗,并取得良好疗效。本文主要针对BNCT药物研究、生物学机制、潜在优势、临床应用进行综述。     

快中子放疗同时硼中子俘获治疗

中子用于肿瘤的临床治疗主要有两种形式:快中子放疗(FNRT)和硼中子俘获治疗(BNCT)。中子优越的放射生物学特性可以更有效地杀伤某些肿瘤,但是这两种治疗手段都存在着某些尚待解决的问题。将两种治疗结合起来可能产生临床上更理想的治疗增益,因此有必要对FNRT同时BNCT做进一步的实验室及临床方面的研究。本文将从以下四个方面讨论中子放疗的情况;①快中子放疗。②硼中子俘获治疗。③BNCT与FNRT同时进行可增强快中子放疗的效果。④今后研究的方向。这里重点探讨BNCT增加FNRT有效的物理及生物剂量问题。     

Translational boron neutron capture therapy (BNCT) studies for the treatment of tumors in lung

Abstract

Purpose: Boron neutron capture therapy (BNCT) combines selective accumulation of ¹⁰B carriers in tumor tissue with subsequent neutron irradiation. BNCT has been proposed for the treatment of multiple, non-resectable, diffuse tumors in lung. The aim of the present study was to evaluate the therapeutic efficacy and toxicity of BNCT in an experimental model of lung metastases of colon carcinoma in BDIX rats and perform complementary survival studies.

Materials and methods: We evaluated tumor control and toxicity in lung 2?weeks post-BNCT at 2 dose levels, including 5 experimental groups per dose level: T0 (euthanized pre-treatment), Boronophenylalanine-BNCT (BPA-BNCT), BPA?+?Sodium decahydrodecaborate-BNCT ((BPA?+?GB-10)-BNCT), Beam only (BO) and Sham (no treatment, same manipulation). Tumor response was assessed employing macroscopic and microscopic end-points. An additional experiment was performed to evaluate survival and oxygen saturation in blood.

Results and conclusions: No dose-limiting signs of short/medium-term toxicity were observed in lung. All end-points revealed statistically significant BNCT-induced tumor control vs Sham at both dose levels. The survival experiment showed a statistically significant 45% increase in post-treatment survival time in the BNCT group (48?days) versus Sham (33?days). These data consistently revealed growth suppression of lung metastases by BNCT with no manifest lung toxicity.

• Highlights

• Boron Neutron Capture Therapy suppresses growth of experimental lung metastases

• No BNCT-induced short/medium-term toxicity in lung is associated with tumor control

• Boron Neutron Capture Therapy increased post-treatment survival time by 45%

     

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.     

Feasibility study of SPECT system for online dosimetry imaging in boron neutron capture therapy

A single collimator version of a proposed PG-SPECT system was manufactured and experimentally tested. Combining this experimental data with Monte Carlo simulation, the viability of Ge and CdTe semiconductors detectors was calculated. It was determined that the best detector of the ones compared would be a CdTe detector of 2–3 mm, aided by the benefit of adding a Compton-suppression anti-coincidence timing detector.     

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.     

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。     

Dose estimation for internal organs during boron neutron capture therapy for body-trunk tumors

Radiation doses during boron neutron capture therapy for body-trunk tumors were estimated for various internal organs, using data from patients treated at Kyoto University Research Reactor Institute. Dose–volume histograms were constructed for tissues of the lung, liver, kidney, pancreas, and bowel. For pleural mesothelioma, the target total dose to the normal lung tissues on the diseased side is 5 Gy-Eq in average for the whole lung. It was confirmed that the dose to the liver should be carefully considered in cases of right lung disease.