Neutrons against cancer

The review is devoted to the analysis and generalization of the research carried out during recent years in industrially advanced countries on the use of fast, epithermal, and thermal neutrons for therapy of malignant tumors. Basic facilities for neutron production used for cancer treatment are presented. Optimal parameters of therapeutic beams are described. Techniques using neutrons of different energy regions are discussed. Results and medical treatment efficiency are given. Comparison of the current state of neutron therapy of tumors and alternative treatments with beams of protons and carbon ions has been conducted. Main attention is given to the possibility of the practical use of accumulated experience of application of neutron beams for cancer therapy.     

Evaluation of neutron radiation field in carbon ion therapy

Carbon ions have significant advantages in tumor therapy because of their physical and biological properties. In view of the radiation protection, the safety of patients is the most important issue in therapy processes.Therefore, the effects of the secondary particles produced by the carbon ions in the tumor therapy should be carefully considered, especially for the neutrons. In the present work, the neutron radiation field induced by carbon ions was evaluated by using the FLUKA code. The simulated results of neutron energy spectra and neutron dose was found to be in good agreement with the experiment data. In addition, energy deposition of carbon ions and neutrons in tissue-like media was studied, it is found that the secondary neutron energy deposition is not expected to exceed 1% of the carbon ion energy deposition in a typical treatment.     

Nuclear tracks: present and future perspectives

Current research work related to the development of nuclear tracks comprising: (i) fundamental principles (nuclear track physics and chemistry, as well as development of track detectors and the relevant hard- and software), (ii) development of nuclear instruments and methods (etch track radiometers for ions, neutrons and cosmic rays, radon monitoring devices, radiography and fission track dating) is briefly outlined. The paper concentrates on a literature survey of applications of nuclear tracks in (iii) physical sciences (high-energy physics, nuclear physics and earth sciences), (iv) biomedical sciences (radiation protection, environment, cancer therapy), and (v) technological sciences (materials, nano-technology and nuclear technology).

Presently about 350 papers per year are being published in this field. Increased activity is noted in ion track technology (track-made membranes, modern nano-tech methodology including biological and biological-like samples, nano-electrode bio-electrochemistry, bio-magnetic assays and probes). New applications of nuclear tracks in fundamental (possibility of the detection of neutron quantum states in a gravitational field, nucleus–nucleus interactions, search for new chemical super-heavy elements) and applied science (precise measurements of the behaviour of radiation in human tissue in connection with of long term space missions and treatment of cancer) are surveyed, and possible research in the next decades is presented and examined in this review paper.     

The relative biological effectiveness of a high energy neutron beam for micronuclei induction in T-lymphocytes of different individuals

In assessing the radiation risk of personnel exposed to cosmic radiation fields as it pertains to radiological damage during travel in civilian aircrafts, it is particularly important to know the relative biological effectiveness (RBE) for high energy neutrons. It has been the subject of numerous investigations in recent years using different neutron energies and cytogenetic examinations. Variations in the radiosensitivity of white blood cells for different individuals are likely to influence the estimate of the relative biological effectiveness for high energy neutrons. This as such observations have been noted in the response of different cancer cell lines with varying inherent sensitivities. In this work the radiosensitivities of T-lymphocytes of different individuals to the p(66)/Be neutron beam at iThemba LABS were measured using micronuclei formations and compared to that noted following exposure to ⁶⁰Co γ-rays. The principle objective of this investigation was to establish if a relationship between neutron RBE and variation in biological response to ⁶⁰Co γ-rays for lymphocytes from different individuals could be determined. Peripheral blood samples were collected from four healthy donors and isolated lymphocytes were exposed to different doses of ⁶⁰Co γ-rays (1–5 Gy) and p(66)/Be neutrons (0.5–2.5 Gy). One sample per donor was not exposed to radiation and served as a control. Lymphocytes were stimulated using PHA and cultured to induce micronuclei in cytokinesis-blocked cells. Micronuclei yields were numerated using fluorescent microscopy. Radiosensitivities and RBE values were calculated from the fitted parameters describing the micronuclei frequency dose response data. Dissimilar dose response curves for different donors were observed reflecting varying inherent sensitivities to both neutron and gamma radiation. A clear reduction in the dose limiting RBE_M is noted for donors with lymphocytes more sensitive to γ-rays (p = 0.032, R² = 0.94). Unlike observations made with different cancer cell lines exposed to the same clinical neutron beam, the variations in neutron RBE observed in T-lymphocytes of different individuals is related to the cellular radioresistance to photons.     

Tutorial on neutron physics in dosimetry

Almost since the time of the discovery of the neutron more than 70 years ago, efforts have been made to understand the effects of neutron radiation on tissue and, eventually, to use neutrons for cancer treatment. In contrast to charged particle or photon radiation which directly leads to release of electrons, neutrons interact with the nucleus and induce emission of several different types of charged particles such as protons, alpha particles or heavier ions. Therefore, a fundamental understanding of the neutron–nucleus interaction is necessary for dose calculations and treatment planning with the needed accuracy. We will discuss the concepts of dose and kerma, neutron–nucleus interactions and have a brief look at nuclear data needs and experimental facilities and set-ups where such data are measured.     

Dosimetry and spectrometry at accelerator based neutron source for boron neutron capture therapy

An innovative accelerator-based neutron source for boron neutron capture therapy has started operation at the Budker Institute of Nuclear Physics, Novosibirsk. This facility is based on a compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915 MeV protons bombarding a lithium target using ⁷Li(p,n)⁷Be threshold reaction.In the article, techniques to detect neutron and gamma-rays at the facility are described. Gamma radiation is measured with NaI and BGO gamma-spectrometers. The total yield of neutrons is determined by measuring the 477 keV γ-quanta from beryllium decay. For the rough analysis of the generated neutron spectrum we used bubble detectors. As the epithermal neutrons are of interest for neutron capture therapy the NaI detector is used as activation detector. We plan to use a time-of-flight technique for neutron spectra measurement. To realize this technique a new solution of short time neutron generation is proposed.     

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy.The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., ¹²C ions). It is reasonable to assume that the same types of patients would benefit from ¹²C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i.e., moving from neutrons to ¹²C ions and from photons to protons, respectively). An important area of research involves developing criteria to identify specific patients suitable for high-LET radiation. One promising technique is to measure the RBE of the cancer cell population in vitro mainly in head and neck tumors. Modern molecular imaging allows the identification of hypoxic or proliferative regions in the tumor. Special MRI examinations are also able to identify hypoxic regions. A promising predictive test recently initiated, is the study of non-repairable double strand breaks but the utility of the technique needs to be confirmed. The extensive experience with fast neutron therapy can greatly assist the transition to high-LET charged-particle therapy.     

重离子加速器示范装置被动式束流配送系统次级中子特征的蒙特卡罗研究

在碳离子放射治疗中,碳离子束在剂量配送过程中会与束流输运线相互作用,形成以中子辐射为主的外辐射场.由于中子是高LET射线,具有较高的相对生物学效应,减少碳离子放疗中产生的次级中子有助于降低放疗后正常组织并发症几率及二次肿瘤风险.利用蒙特卡罗方法对保守情况(能量为400 MeV/u,多叶光栅完全闭合)下碳离子治疗被动式束...     

基于2.5 MeV质子加速器BNCT装置的中子慢化材料性能模拟研究

基于加速器中子源的硼中子俘获治疗(Boron Neutron Capture Therapy, BNCT)是新一代的放射治疗方法,束流整形体(Beam Shaping Assembly, BSA)作为硼中子俘获治疗装置的重要组成部分,其作用是将中子源中的快中子束流慢化至超热中子能区(0.5 eV~10 keV),并尽可能减少快中子、热中子以及$\gamma $射线的成分,使其满足BNCT用于治疗的中子束要求。本工作基于蒙特卡罗软件包Geant4(Geometry and Tracking),以2.5 MeV,10 mA质子流强的7Li(p, n)7Be中子源为对象,研究分析了AlF₃ 、Fluental、Al₂O₃、Al作为慢化体材料时,不同的厚度对束流出口处的超热中子注量率、超热中子注量与热中子注量比值、快中子成分、$ \gamma $成分所产生的影响。计算表明,当选用厚度为25 cm的AlF₃作为慢化体材料时,经过整形慢化后的超热中子束的束流参数,均满足国际原子能机构(International Atomic Energy Agency, IAEA)的中子束流参数推荐值。     

Microdosimetry for the characterization of the THOR epithermal neutron beam

The epithermal neutron beam of the Tsing Hua Open-pool Reactor (THOR) was constructed for the study of boron neutron capture therapy (BNCT). The THOR epithermal neutron beam was mainly composed of thermal neutrons, fast neutrons, and photons. For fast neutrons and photons, the absorbed dose and the relative biological effectiveness (RBE) were used to characterize radiation dose and radiation quality. The short-ranged alpha particles and lithium ions produced from ¹⁰B(n,α)⁷Li reactions in the BNCT required cellular- and micro-dosimetry characterizations. Due to the non-uniform microdistribution of boron in cells, these characterizations should depend on the source–target geometry. In this case, the geometry-dependent specific cellular dose and lineal energy could be used to describe radiation dose and radiation quality. In the present work, cellular- and micro-dosimetry were studied for the THOR epithermal neutron beam. The specific cellular dose and lineal energy were calculated for thermal neutron-induced α-particles and ⁷Li-ions with different source–target geometry and various cell sizes. Applying the linear energy dependent-biological weighting function, the geometry-dependent RBE of thermal neutron-induced heavy particles was determined. Finally, the effective RBE of the THOR epithermal neutron beam was estimated for tumors and normal tissues of specified ¹⁰B concentrations. This effective RBE should be multiplied by the total absorbed dose to determine the corresponding biological dose required in the treatment planning.     

Monte Carlo calculations and experimental calibrations of Bonner sphere systems with a new cylindrical helium-3 proportional counter

The response functions to mono-energetic neutrons from thermal energy to 20 MeV of eight polyethylene moderating spheres with a cylindrical proportional counter were calculated with the MCNP-4B code for each moderator and confirmed by measurements in wide neutron fields (ISO), as Am–Be and ²⁵²Cf, and with the CANEL and SIGMA IPSN Cadarache (France) facilities, which simulate realistic field and thermal neutron response. With the described spectrometry system, we have carried out neutron measurements at different points from the annular zone inside the containment building of the Vandellòs II Nuclear Power Plant (Tarragona, Spain). The aim of this work is to present the results obtained during the sphere spectrometer development, with reference to the experimental and theoretical aspects and to show that our calculated spectra correspond to points of measurement compared with those obtained using the MORELPA code.     

241Am-Be中子参考辐射的蒙特卡罗模拟研究

研究用于校准场所中子剂量监测仪表的241Am-Be中子参考辐射场计量特性。采用蒙特卡罗方法模拟了空气自由中子参考辐射(FRNR),GB/T 14055规定的最小尺寸中子参考辐射(SRNR)和实际中子参考辐射(ARNR)中不同检验点处中子周围剂量当量率、散射中子占比和能谱分布特征。研究结果表明,空气对FRNR中的剂量率和能谱分布影响小,近似为理想中子参考辐射;采用5%含硼聚乙烯作屏蔽的最小尺寸SRNR可减少热中子,降低散射中子占比,影锥法不适用于小尺寸中子参考辐射中对散射中子的修正;ARNR中的散射中子更少、占比更低,影锥法所得散射中子占比与理论值基本一致。     

Preliminary investigations of Monte Carlo simulations of neutron energy and let spectra for fast neutron therapy facilities

No fast neutron therapy facility has been built with optimized beam quality based on a thorough understanding of the neutron spectrum and its resulting biological effectiveness. A study has been initiated to provide the information necessary for such an optimization. Monte Carlo studies will be used to simulate neutron energy spectra and LET spectra. These studies will be bench-marked with data taken at existing fast neutron therapy facilities. Results will also be compared with radiobiological studies to further support beam quality optimization. These simulations, anchored by this data, will then be used to determine what parameters might be optimized to take full advantage of the unique LET properties of fast neutron beams.This paper will present preliminary work in generating energy and LET spectra for the Fermilab fast neutron therapy facility.     

微束技术在放射生物学中的应用

微束装置可以为生命科学研究提供微米定位、剂量特定的电离辐射,在生物体内的电离辐射靶物质及其敏感度、靶物质的损伤及修复机制研究中具有独特的作用。概述了生物微束装置和实验技术的发展及其在低剂量辐射效应、旁观者效应、信号传导研究中的主要应用;介绍了中国科学院近代物理研究所（IMP）重离子微束装置,该装置可以提供能量7~ 80 MeV/u、传能线密度为30~ 3000 keV/μm的重离子微束,实现了活细胞辐照和在线观察、小鼠定位辐照的实验技术;利用IMP微束装置在重离子诱导旁效应实验、小鼠下丘脑重离子辐照效应和DNA损伤快速修复动态等方面取得了一些实验成果。The microbeam facility can provide micrometer scale localized and predefined ionizing radiation in the life science study, and the microbeam techniques play a unique role in determining the target substances of ionizing radiation, as well as in the study of radiation sensitivity, mechanisms of radiation damage response and repair. This paper summarizes the technical developments of biological microbeam facilities and their applications in the studies of low-dose radiation effect, bystander effect and cellular signaling. This paper also introduces the recent developments at the heavy-ion microbeam facility in the Institute of Modern Physics (IMP), which can provide heavy ion microbeam irradiation with energy of 7~80 MeV/u and LET of 30~3000 keV/μm. The facility can perform radiobiological irradiation and online investigation in living cells and mice, including bystander effect study, sleeping system influence after irradiation to mice hypothalamus and the recruitment dynamics of XRCC1 protein.     

Radiation Protection of CSR

The construction of CSR (cooling storage ring) which includes a main ring (CSRm) and an experimental ring (CSRe) will be finished at the end of 2005. Heavy ions of carbon to uranium will be accelerated up to 900MeV/u and 400MeV/u at intensity of 10⁸ pps. The HIRFL (heavy ion research facility in Lanzhou) will be used as the injector. For the shielding design of CSR, the secondary neutrons due to the ion beam loss, their spectra and angular distributions were estimated based on the experimental results. The dose equivalent outside the shielding surface and in the surrounding environment and the neutron skyshine dose equivalent were also estimated in this study. The experimental result, neutron yield, spectrum and angular distribution for 400MeV/u ¹²C+Cu reaction were used for estimating the source term of shielding design. It is found that the most important environmental radiation impact component of CSR is the skyshine neutrons.     

CSR的辐射防护

CSR(cooling storage ring)按计划将于2005年底建成调束,届时从¹²C到²³⁸U的重离子将可以分别被加速到900和400MeV的能量. HIRFL(兰州重离子加速器Heavy Ion Research Facility in Lanzhou)将 用作CSR的注入器. 为了CSR的屏蔽设计,本文利用现有的实验数据计算了由于束流损失产生的中子及其能谱、角分布,同时也估算了屏蔽体外表面的中子剂量、环境中子剂量及天空返照中子剂量. 在源项计算中使用了400MeV/u ¹²C+Cu反应的中子产额、能谱、角分布的实验数据. 计算表明, CSR对环境剂量影响最大的是天空返照中子.     

Research into accelerator driven systems using particle track detectors

In the interaction of relativistic protons with heavy and extended targets such as lead, large number of neutrons is produced in the course of the so-called spallation process. These neutrons can be used to drive a sub-critical nuclear assembly for energy generation and/or for the transmutation of the long-lived nuclear waste isotopes to environmentally safer nuclear species. Such nuclear assemblies are referred to as accelerator driven systems (ADS).

Knowledge of the neutron yield in the spallation process and an understanding of the behaviour of these neutrons in the desired sub-critical assembly are the most important and determining factors in the design and operation of these systems. Many parameters related to the neutronics of an ADS can be studied qualitatively as well as quantitatively using solid-state nuclear track detectors (SSNTD). In some circumstances SSNTDs provide the best and the most logical detector option for these investigations.

In this paper applications of the SSNTDs into research related to ADS are discussed and some experimental and theoretical results presented.     

Study of neutron dose equivalent at the HIRFL deep tumor therapy terminal

The secondary neutron fields at the deep tumor therapy terminal at HIRFL(Heavy Ion Research Facility in Lanzhou) were investigated. The distributions of neutron ambient dose equivalent were measured with a FHT762Wendi-II neutron ambient dose equivalent meter as ~(12)C ions with energies of 165, 207, 270, and 350 Me V/u were bombarded on thick tissue-like targets. The thickness of targets used in the experiments was larger than the range of the carbon ions. The neutron spectra and dose equivalent were simulated by using FLUKA code, and the results agree well with the experimental data. The experiment results showed that the neutron dose produced by fragmentation reactions in tissue can be neglected in carbon-ion therapy, even considering their enhanced biological effectiveness.These results are also valuable for radiation protection, especially in the shielding design of high energy heavy ion medical machines.     

Characteristics of a stilbene scintillation crystal in a neutron spectrometer

Various organic scintillators are commonly used as the detecting material for neutrons, but these detectors are less sensitive to gamma rays. In particular, stilbene crystals and BC501A (NE213, EJ301) have good pulse-shape discrimination (PSD) between neutron and gamma-ray events, and have been selected as the media for fast-neutron detection among the organic, inorganic and plastic materials in a mixed radiation field. Although some of the scintillation characteristics of stilbene crystals have been studied, the detailed scintillation characteristics of the crystal are not completely understood. In this study, the light yield, decay time and pulse shape discrimination capability of a stilbene crystal were measured because this crystal is an optimized detector in a large flux of neutrons such as those might be found in cyclotron and charged particle accelerator facilities. The pulse-shape discrimination of neutrons and gamma rays with a stilbene crystal was measured using a ²⁵²Cf neutron source at room temperature. A neutron tagger module was used for the neutron and gamma separation using the charge comparison method in real time. The total pulse width for the charge integration and the delay from the peak-to tail start time were optimized for a better neutron and gamma separation. The relative light yield and decay time of the stilbene crystal scintillator were also measured.     

Use of CR-39 solid state nuclear track detector in neutron personnel monitoring

Neutron sources like ²⁴¹Am–Be, ²³⁹Pu–Be, ²⁵²Cf and 14.6 MeV neutron generator are being used in oil exploration industries as well as in research institutions. While handling these neutron sources, personnel may be exposed to neutrons. Also personnel working in reactors, accelerators may receive dose from neutrons. These exposed individuals need to be monitored regularly for measurement of neutron doses. The individual neutron doses can be estimated by using Kodak NTA films and CR-39 Solid State Nuclear Track Detector with a polyethylene radiator to increase sensitivity in front in holder. Nearly 1450 personnel are being monitored regularly throughout the country on a quarterly basis. In India, the monitoring system adopted for individual neutron dose estimation having energy from 100 keV and above is described in this paper. Background counts of 0.20 mSv could be measured with CR-39 SSNTD foil system and it has been successfully introduced for Fast Neutron Personnel Monitoring for the country.