重离子束用于肿瘤放射治疗的基础理论

通过与低传能线密度辐射治疗对比分析建立了重离子束肿瘤放射治疗的基础理论,提出了一些提高重离子束放射治疗疗效和减少对正常组织损伤的技术措施,旨在为已开展的重离子治癌临床研究提供理论依据． The basic theory of tumor radiotherapy with heavy ion beam was introduced in contrast to low LET irradiation therapy. Some useful methods are also suggested to improve the curative effect of heavy ion therapy and to spare the normal tissue around the tumor.     

重离子治癌的磁扫描照射野形成法

在论述重离子治癌照射的基本思想及其特点的基础上,着重对磁扫描照射野形成的两种技术路线——点扫描和栅扫描的优缺点进行了分析阐述.初步给出了 HIRFL上的重离子治癌终端磁扫描相关参数. The basic principle and characteristic of irradiation in heavy ion radiotherapy are introduced. Based on the basic principle and characteristic of irradiation in heavy ion radiotherapy, two magnetic scan methods for creating uniform irradiation field--the spot scan and the raster scan, are compared briefly. The parameter requests to the magnetic scanning system of the heavy ion radiotherapy facility planned in IMP(Institute of Modern Physics) are presented.     

重离子束适形放射治疗技术

重离子束适形放射治疗技术主要包括束流配送系统和治疗计划系统等 .前者是实现重离子束适形放射治疗的硬件设施 ,后者为适形治疗的软件支撑系统 ,两者缺一不可 .鉴于重离子束与物质相互作用在物理学及生物学效应上表现出的特殊性,重离子束治癌中特别引入了面向生物学效应的适形治疗和束流的正电子断层在线监控技术. The conformal radiotherapy techniques mainly include the two systems that are beam delivery and treatment planning. The formal is the hardware basis while the later is the software supplement for heavy ion conformal therapy, they are dependent on each other to realize the cancer conformal therapy with heavy ion beam. Because of the specificities of interaction between heavy ion and target on both physics and biological effects, the heavy ion cancer therapy especially involves...     

Neutron dose measurement in carbon ion radiation therapy at HIRFL （IMP）

For radiation protection purposes, the neutron dose in carbon ion radiation therapy at the HIRFL （Heavy Ion Research Facility in Lanzhou） was investigated. The neutron dose from primary ^12C ions with a specific energy of 100 MeV/u delivered from SSC was roughly measured with a standard Anderson-Broun rem-meter using a polyethylene target at various distances. The result shows that a maximum neutron dose contribution of 19 mSv in a typically surface tumor treatment was obtained, which is less than 1% of the planed heavy ion dose and is in reasonable agreement with other reports. Also the T-ray dose was measured in this experiment using a thermo luminescent detector.     

Incident particle range dependence of radiation damage in a power bipolar junction transistor

The characteristic degradations in silicon NPN bipolar junction transistors(BJTs) of type 3DD155 are examined under the irradiations of 25-MeV carbon(C),40-MeV silicon(Si),and 40-MeV chlorine(Cl) ions respectively.Different electrical parameters are measured in-situ during the exposure of heavy ions.The experimental data shows that the changes in the reciprocal of the gain variation((1/β)) of 3DD155 transistors irradiated respectively by 25-MeV C,40-MeV Si,and 40-MeV Cl ions each present a nonlinear behaviour at a low fluence and a linear response at a high fluence.The(1/β) of 3DD155 BJT irradiated by 25-MeV C ions is greatest at a given fluence,a little smaller when the device is irradiated by 40-MeV Si ions,and smallest in the case of the 40-MeV Cl ions irradiation.The measured and calculated results clearly show that the range of heavy ions in the base region of BJT affects the level of radiation damage.     

重离子束治癌

本文回顾了辐射治癌的历史发展和国内外动态,讨论了重离子束与常规辐射相比在肿瘤治疗上的优势,提出了为治疗应用的重离子束的主要参数以及在兰州重离子研究装置（ＨＩＲＦＬ）拟建的冷却储存环（ＣＳＲ）上建立治疗实验室的初步考虑． Historical background and trends at home and abroad for radiation therapy arelooked back in the paper. The advantages of heavy ion beam in comparision with conventional radiation in tumour treatment are discussed. The main parameters of heavy ion beams fortherapy application and a tentative idea constructing treatment rooms at Cooling StorageRing(CSR) of Heavy Ion Research Facility in Lanzhou (HIRFL) are proposed.     

辐照诱导人正常肝细胞系HL-7702 细胞远后的微卫星不稳定性

采用高传能线密度(LET) 的12C6+离子束和低LET 的X 射线辐照人正常肝细胞系HL-7702 细胞,利用微卫星不稳定性(MSI) 检测来分析直接受照射细胞和通过转移培养基方式旁细胞传代八代子细胞以MSI 表征的远后效应。实验结果表明,12C6+离子束诱导的远后效应较X射线的低;旁细胞的远后效应较直接受照射细胞的高;辐射引起的MSI 与杂合性丢失(LOH) 的发生率具有位点特异性。结果提示,重离子放射治疗较X 射线放射治疗对正常组织引发的辐射风险要小,可通过对MSI 高发位点的筛选来评估放疗后患者长期生存状况和二次癌症发生风险。Human normal liver cell line HL-7702 cells were irradiated with high linear energy transfer (LET) 12C6+ ions and low-LET X-rays, respectively. Delayed effect in terms of microsatellite instability (MSI) in progenies of the directly irradiated cells and bystander cells, obtained in the way of medium transfer at the 8th passage postirradiation,were examined. The delayed effect induced by the high-LET 12C6+ ions was different from that induced by the low-LET X-rays, and a higher incidence of MSI was observed in the progenies of the cells after exposure to the X-rays than to the 12C6+ ions. We also found that the delayed effect in the progenies of the bystander cells was much more severe than thoseof directly irradiated cells. Furthermore, the events of MSI and loss of heterozygosity (LOH) induced by the ionizing radiations were not randomly distributed throughout the genome and specific loci existed indeed. These results imply that the radiation risk to normal tissues is lower in heavy ion therapy than in conventional X-ray radiotherapy, and the analysis of microsatellite loci with MSI high frequency occurrence can be applied to access long-term survival condition and second cancer risk for the patients after radiotherapy.     

碳离子辐射诱导秀丽隐杆线虫生殖细胞凋亡研究

重离子辐射具有独特的深度剂量分布和较高的相对生物学效应,被认为是理想的放疗手段。重离子的生物学效应在径迹形成过程中由多个物理参量共同决定,而这些物理参量和离子入射深度紧密相关,因此明确离子不同入射深度的生物学效应对重离子肿瘤放疗方案的设计和优化有着重要的理论和应用价值。使用兰州重离子研究装置HIRFL-CSRe 终端的碳离子束作为辐射源,以活体模式动物线虫作为实验对象,以线虫生殖细胞的凋亡水平作为生物学检测终点,研究了10 和20 Gy 碳离子辐射在辐射的入口、坪区和峰区的当代生物学效应和对后代个体基因组不稳定性的影响。结果表明:10 和20 Gy 碳离子辐射在三个不同的辐照区域内均显著增加了辐射当代的线虫生殖腺细胞的凋亡水平,并表现出一定的辐射区域和辐射剂量依赖性。同时,辐射诱导的后代个体基因组不稳定性也表现出一定的辐射区域和辐射剂量相关性。Heavy ion irradiation is a perfect means in radio-therapy due to its special depth dose distribution and high relative biological effects. The biological effects of heavy ion irradiation are determined by some major physical parameters, and vary along the tracks of heavy ions. Therefore, it is very significant for the tumor radio-therapy to investigate the biological effects along whole range of heavy ion radiation. In the present study, Caenorhabditis elegans, a model in vivo, was irradiated by carbon ion beams from HCRFL-CSRe, The level of germ cell apoptosis of worms was used as a checking endpoint for DNA damage, the effects of carbon irradiation located in the entrance, plateau and peak regions on the genomic instability of the irradiated worm and their progeny were detected. The results showed that the 10 and 20 Gy of carbon ion radiations led to the increased germ cell apoptosis in irradiated worms and these effects depend on the worm location along the range of carbon ions and the irradiation dosage. The results also suggested that heavy ion irradiation induced the up-regulated genomic instability in their progeny, and might be related to both the irradiation dose and the irradiated location.     

利用HIRFL高能重离子束的核能材料辐照损伤研究

载能重离子与高能中子在材料中能够产生相似的级联碰撞损伤,加之重离子具有大的离位损伤截面和在材料样品中低的感生放射性,载能重离子束成为模拟先进核能装置内部结构材料辐照损伤的重要手段。HIRFL能区的重离子在结构材料中的射程一般远大于晶粒尺寸,因此能够产生材料体损伤,借助小样品技术可以获得材料力学性能变化（尤其辐照脆化）的有用信息,为探讨材料辐照损伤微结构和宏观力学性能变化的关联提供了重要条件。本文简要介绍了近年来我们基于HIRFL高能离子束开展的聚变堆候选材料辐照损伤的研究,包括低活化钢的辐照脆化行为、氧化物弥散强化（ODS）铁素体钢的结构优化对于抗辐照性能的影响、不同载能粒子辐照条件下铁素体/马氏体钢的辐照肿胀数据的关联,以及高能重离子辐照的钨材料中氢同位素的滞留行为。研究表明,结合特殊的测试技术及数据分析方法,高能重离子可作为核能结构材料辐照损伤研究及评估的有效手段。Because of the similarity in cascade damage structure in materials produced by energetic heavy ions and by fast neutrons, and the high displacement rate and low induced radioactivity of samples by heavy ions, heavy ion beam becomes an important tool to simulate radiation damage by energetic neutrons in materials in advanced nuclear energy systems. The ranges of heavy ions provided by HIRFL (Heavy Ion Research Facility in Lanzhou) are generally much larger than the mean dimensions of grains in alloys candidate to advanced nuclear reactors, and is capable of producing radiation damage in bulk scale. It therefore makes possible the evaluation of change of mechanical properties including the radiation induced embrittlement from the irradiated specimens by using miniaturized specimen techniques. In the present paper, we provide an introduction of our recent studies of radiation damage of materials candidate to future fusion reactors by utilizing heavy ion beams in HIRFL.The studies include issues as follows:ductility loss of RAFM steels causes by high-energy Ne ions, impact of oxide dispersoids on the radiation resistance of ODS ferritic steels, correlation of void swelling of ferritic/martensitic steels under different particle irradiation, and behavior of deuterium retention in tungsten under irradiation with high-energy heavy ions. The results show that high-energy heavy ions can be used as a tool to efficiently investigate or evaluate radiation damage in structure materials if combined with some special test techniques and data analysis.     

大分割碳离子放射治疗中相对生物学效应与剂量依赖关系的研究

应用碳离子束进行大分割放射治疗从而缩短治疗周期是碳离子束治疗的优势之一。为研究大分割放疗增加单次照射剂量后,碳离子束相对生物学效应（RBE）的变化,应用细胞存活线性平方（LQ）模型推导出RBE与剂量的依赖关系。基于此关系研究了具有不同辐射敏感性的肿瘤细胞和正常组织细胞RBE随剂量的变化。结果表明,在0~20 Gy范围内,不论肿瘤细胞与正常组织细胞具有怎样的辐射敏感性,肿瘤细胞的RBE值始终大于正常组织细胞。此外,基于理论推导和对相关实验数据的分析,证实了RBE随剂量增加而递增现象的存在。这些结果对应用碳离子束进行大分割放射治疗具有重要的指导作用。Short treatment course due to the suitability of hypofractionated regimen for carbon ion beam is one of the advantages of carbon ion radiotherapy. To study the dependence of relative biological effectiveness (RBE) on dose, the relationship between RBE and dose was deduced through the linear-quadratic (LQ) model. Based on the relationship, the change of RBE of tumor cells and normal tissue cells with different radiosensitivities with dose was studied. The results showed that the RBE value of tumor cells was always greater than that of normal tissue cells in the dose range of 0~20 Gy, regardless of the radiosensitivity of tumor and normal tissue cells. In addition, based on theoretical deduction and analysis of the relevant experimental data, the existence of RBE increase with increasing dose was verified. These results are of great significance for conducting hypofractionated radiotherapy with carbon ion beam.     

Heavy-ion cancer therapy

The HIMAC Heavy-Ion Medical Accelerator in Chiba was completed in 1993, and clinical trials of particle radiotherapy for cancer were started using carbon beams accelerated by HIMAC in 1994. Since then, about 2200 patients have been treated in the carbon radiotherapy up to the end of February 2005. A heavy-ion beam generates a Bragg peak in a medium, and it provides biological effects of high RBE and low OER in the Bragg peak region. In heavy-ion radiotherapy, therefore, the beam delivers a high radiation dose to a target volume highly locally. These are excellent advantages for radiotherapy over the case of X-rays. The clinical trials have proved that carbon radiotherapy brings various good results.     

利用基于~1H NMR的代谢组学分析研究重离子辐射对大鼠额叶皮质区的影响

太空辐射尤其是重离子辐射可造成DNA的破坏、细胞死亡、以及一些癌症的发生, 是人类深空探索进程中急需克服的难题. 本文通过重离子加速器产生 ~(12)C~(6+)重离子束对大鼠头部进行一定剂量的辐射, 模拟空间重离子辐射对中枢神经系统(CNS)的生物学效应. 采用基于 ~1H NMR的代谢组学方法对辐射大鼠大脑额叶皮质区进行了测定分析, 结合数据的统计分析和检验, 发现了包括一些重要CNS神经递质在内的代谢物含量发生明显变化. 这些代谢物主要为: 牛磺酸、乳酸、谷氨酸、 4-氨基丁酸、以及磷酸胆碱等. 结合差异蛋白质组结果分析, 包括4-氨基丁酸、谷氨酸、乳酸、牛磺酸等在内的代谢物参与的主要生物途径, 如神经递质的合成途径, 以及神经递质受体介导的信号途径可能受重离子辐射的负面影响. 这些发现将为进一步阐明重离子辐射效应的分子机制提供有利信息, 从而为从生物学途径探寻有效重离子辐射防护措施提供依据.     

利用基于~1H NMR的代谢组学分析研究重离子辐射对大鼠额叶皮质区的影响

太空辐射尤其是重离子辐射可造成DNA的破坏、细胞死亡、以及一些癌症的发生,是人类深空探索进程中急需克服的难题. 本文通过重离子加速器产生¹²C⁶⁺重离子束对大鼠头部进行一定剂量的辐射,模拟空间重离子辐射对中枢神经系统(CNS)的生物学效应. 采用基于¹H NMR的代谢组学方法对辐射大鼠大脑额叶皮质区进行了测定分析,结合数据的统计分析和检验,发现了包括一些重要CNS神经递质在内的代谢物含量发生明显变化. 这些代谢物主要为：牛磺酸、乳酸、谷氨酸、4-氨基丁酸、以及磷酸胆碱等. 结合差异蛋白质组结果分析,包括4-氨基丁酸、谷氨酸、乳酸、牛磺酸等在内的代谢物参与的主要生物途径,如神经递质的合成途径,以及神经递质受体介导的信号途径可能受重离子辐射的负面影响. 这些发现将为进一步阐明重离子辐射效应的分子机制提供有利信息,从而为从生物学途径探寻有效重离子辐射防护措施提供依据.     

Experimental verification of therapeutic doses for the superficially-placed tumor radiotherapy with heavy ions at HIRFL

Up to now, clinical trials of heavy-ion radiotherapy for superficially placed tumors have been carried out for six times and over 60 selected patients have been treated with 80--100 MeV/u carbon ions supplied by the Heavy Ion Research Facility in Lanzhou （HIRFL） at the Institute of Modern Physics, Chinese Academy of Sciences since November, 2006. A passive irradiation system and a dose optimization method for radiotherapy with carbon-ion beams have been developed. Experimental verification of longitudinally therapeutic dose distributions was conducted under the condition of simulating patient treatment in the therapy terminal at HIRFL. The measured depth-dose distributions basically coincide with the expected ones. These results indicate that the irradiation system and the dose optimization method are effective in the ongoing carbon-ion radiotherapy for shallow-seated tumors at HIRFL.     

碳离子辐照对神经胶质瘤干细胞杀伤的研究

虽然重离子束治癌已经被证明有着射程精确、入口坪区剂量小、相对生物学效应高等显著优点,但重离子辐照对肿瘤干细胞所产生的辐射生物学效应特性依旧不明确。本研究使用人源神经胶质瘤干细胞来研究在面对肿瘤干细胞时,重离子相对于传统X射线是否有明显的生物学优势。实验结果证明,在神经胶质瘤干细胞中,2 Gy碳离子造成的DNA损伤的修复率比X射线造成的损伤修复率要低;MTT实验则证明经过碳离子辐照的肿瘤干细胞活力要比X射线辐照的肿瘤干细胞低得多。综上所述,面对神经胶质瘤干细胞,碳离子能更有效地靶向肿瘤干细胞从而相对于传统X射线有明显的生物学优势。这些发现对于更好地理解重离子束治癌相关的生物学效应有重要的作用。Though heavy-ion therapy has demonstrated significant benefits such as well-defined range, small entrance dose and high relative biological effectiveness, the characteristics of radio-biological effects on cancer stem cells induced by heavy-ion treatment is not completely clear. In this paper, we used human glioma cancer stem cells to investigate whether heavy ions offered a biological advantage, by effectively targeting cancer stem cells, in comparison to conventional X-rays. Our results showed that the repair rate of DNA damage generated by 2 Gy of carbon ions was lower than that generated by X-rays in glioma stem cells. MTT assay showed that the viability of cancer stem cells irradiated by carbon ions was significant lower than that irradiated by X-rays. Taken together, carbon ions showed a biological advantage over X-rays by effectively targeting glioma cancer stem cells. These findings have significant importance in understanding the biological effects related to heavy-ion therapy.     

Experimental verification of therapeutic doses for the superficially-placed tumor radiotherapy with heavy ions at HIRFL

Up to now, clinical trials of heavy-ion radiotherapy for superficially placed tumors have been carried out for six times and over 60 selected patients have been treated with 80--100 MeV/u carbon ions supplied by the Heavy Ion Research Facility in Lanzhou (HIRFL) at the Institute of Modern Physics, Chinese Academy of Sciences since November, 2006. A passive irradiation system and a dose optimization method for radiotherapy with carbon-ion beams have been developed. Experimental verification of longitudinally therapeutic dose distributions was conducted under the condition of simulating patient treatment in the therapy terminal at HIRFL. The measured depth-dose distributions basically coincide with the expected ones. These results indicate that the irradiation system and the dose optimization method are effective in the ongoing carbon-ion radiotherapy for shallow-seated tumors at HIRFL.     

中能重离子微束辐照装置的研制

微束辐照装置是将辐照样品的束斑缩小到微米量级, 能够对辐照粒子进行准确定位和精确计数的实验平台, 是开展辐照材料学、辐照生物学、辐照生物医学以及微加工的有力工具. 中国科学院近代物理研究所(IMP)正在研制中能重离子微束辐照装置. 该装置以兰州重离子加速器(HIRFL)系统提供的中能和低能重离子束流为基础, 采用磁聚焦方式形成微米束. 束运线上两台铅垂方向的偏转磁铁辅以四极磁铁构成对称消色差系统, 将束流导向地下室, 再用高梯度的三组合四极透镜强聚焦形成微米束斑, 在真空中或大气中辐照样品. 它将成为国内首台能够提供从低能(10MeV/u)到中能(100MeV/u)的重离子微束的公共实验平台, 用于定位、定量照射靶物质(生物细胞、组织或其它非生物材料等), 有助于深入揭示重离子与物质相互作用的本质, 也为探索重离子辐照效应的应用提供新的手段.     

NIRS的ECR离子源现状

Four ECR ion sources have been operated in National Institute of Radiological Sciences(NIRS). Two ECR ion sources supply various ion species for the Heavy Ion Medical Accelerator in Chiba(HIMAC). The 10GHz NIRS-ECR ion source mainly produces C~(2 ) ions for the heavy-ion therapy.Ions of Si,Ar,Fe,Kr and Xe are usually produced by the 18GHz NIRS-HEC ion source for physical and biological experiments.The other two compact ECR ion sources with all permanent magnet configuration have been developed for the new generation carbon therapy facility.One of these,the Kei-source,is a prototype which has been installed to the NIRS-930 cyclotron for axial injection.The other source,Kei2-source,is a demonstration source and utilized for the new generation Linac.In addition,both Kei sources have been used to study fundamental properties. In this paper,present status of the ion sources and recent developments are reported.     

IMP-8 observations of the spectra, composition, and variability of solar heavy ions at high energies relevant to manned space missions.

In more than 25 years of almost continuous observations, the University of Chicago's Cosmic Ray Telescope (CRT) on IMP-8 has amassed a unique database on high-energy solar heavy ions of potential relevance to manned spaceflight. In the very largest particle events, IMP-8/CRT has even observed solar Fe ions above the Galactic cosmic ray background up to approximately 800 MeV/nucleon, an energy sufficiently high to penetrate nearly 25 g/cm2 of shielding. IMP-8/CRT observations show that high-energy heavy-ion spectra are often surprisingly hard power laws, without the exponential roll-offs suggested by stochastic acceleration fits to lower energy measurements alone. Also, in many solar particle events the Fe/O ratio grows with increasing energy, contrary to the notion that ions with higher mass-to-charge ratios should be less abundant at higher energies. Previous studies of radiation hazards for manned spaceflight have often assumed heavy-ion composition and steeply-falling energy spectra inconsistent with these observations. Conclusions based on such studies should therefore be re-assessed. The significant event-to-event variability observed in the high-energy solar heavy ions also has important implications for strategies in building probabilistic models of solar particle radiation hazards.     

Photonuclear reactions: Modern status of the data

Photonuclear reaction data play an important role in basic and applied research. Radiation shielding design, radiation transport analysis, activation analysis, astrophysical nucleosynthesis, safeguards and inspection technologies, human body radiotherapy absorbed dose calculations, beam monitoring in heavy-ion dissociation research at ultrarelativistic energies, etc., could be mentioned. However, there exist quite evident systematic discrepancies in both shapes and magnitudes between photonuclear cross sections measured in various laboratories. These discrepancies noticeably reduce the accuracy and reliability of data. A systematic overview of various types of data contained in the international database is given. The modern status of the data is discussed. The reasons for significant discrepancies between various photonuclear data are analyzed and methods to reduce them are suggested.