高能X射线肿瘤照射靶区的生物剂量验证的可行性研究

目的:研究MM50加速器高能X射线放疗患者时光核反应产生的正电子发射核在PET/CT的显象技术及显象信息,探讨用该信息对照射的肿瘤靶区准确度和剂量分布进行活体的生物学验证。材料与方法:当用高能光子线照射肿瘤时,其与人体的主要组成元素碳C、氧O、氮N等进行光核反应,在照射区会产生可发射正电子的11C,15O,13N等核素,用正电子发射断层扫描仪PET/CT立即扫描照射后的病人,11C,15O,13N等发射的正电子即可在功能影像或分子生物学影像设备PET/CT上显像。根据显像的位置和强度便可分析推断和验证肿瘤照射的生物学位置和生物学剂量,从而真正意义上实现精确的生物适形放疗和验证。用与人体组成类似的有机玻璃头模实验,按常规放射治疗程序,先在PET/CT进行肿瘤的CT定位,之后用治疗计划系统TPS设计三野照射计划,按计划在MM50加速器上用三组不同能量(10MV,25MV,50MV)和剂量为1Gy～10Gy的X射线进行照射。由于碳C、氧O是人体最主要的组成元素,所以我们只研究11C,15O等核素的显像。对11C和15O,PET/CT上分别扫描20min或2min～5min获取正电子核素显像及显像位置、强度分布等信息。MM50是IBA公司医用跑道式电子回旋加速器,束流能量范围10MeV～50MeV,三维治疗计划设计系统是核通公司的3D治疗计划系统TPP3.2,美国GE公司的Discovery LSⅡ PET/CT,用于肿瘤定位和核医学图像扫描及数据处理。结果:10MV X射线,放疗后不能产生光核反应;25MV X射线可产生光核反应,但需要较大的照射剂量,方能获得有意义的信息。对50MV X射线,2Gy～4Gy的常规放疗剂量即可获得11C,15O的正电子显像图及强度分布等信息,10Gy的剂量即可清楚获得15O和11C的正电子显像图及强度分布等信息。结论:MM50加速器50MV X射线放疗病人时光核反应产生正电子发射核可在PET/CT上显像,显像的位置和强度分布可用来对射线照射肿瘤靶区的准确度和照射剂量进行生物学验证,但要获得定量关系还需做大量工作。     

最佳适形野边距的决定因素和求取方法

目的：探讨最佳适形野边距(block aperture margin，BAM)的决定因素和求取方法。方法：采用三维治疗计划系统(three-dimensional treatment planning system,3-D TPS)，测算出头部和胸部常用放疗条件下“建议射野边距”(P90／50)；根据“建议射野边距”，计算出采用不同BAM时，6MeV X线三野照射头部靶区的剂量分布及15MeV X线四野照射胸部靶区的剂量分布。确定其中符合临床剂量要求，治疗体积在大小和形状上与计划靶区适形程度最好者所采用的BAM为最佳BAM。结果：头部靶区6MeV X线三野照射的最佳BAM为5-7mm，胸部靶区15MeV X线四野照射的最佳BAM为7-10mm。结论：最佳BAM的决定因素复杂，最终求取需三维剂量分布计算。     

模拟调强放疗照射离体细胞的质量保证

目的：在模拟调强放疗方式照射细胞的过程中，保证细胞按调强方式被照射，照射剂量准确。方法：在细胞培养瓶中装满细胞培养液，水平固定在标准水箱（30cm×30cm×30cm）电离室横梁上，在水箱中加水到电离室上方5cm，用CT机（philips brilliance bigbor CT）扫描获取图像，传到计划系统（ECLIPSE 7．0）中；再用一个空的培养瓶替换装满培养液的培养瓶，重新用CT机扫描，获取图像，传到计划系统中。采用先设野中野后合并野中野的设计方法，设计模拟调强照射计划，设定电离室处的吸收剂量400cGy。再把此水箱放到加速器（Varian 600-C／D）下，按设计的模拟调强照射计划进行照射，同时用电离室（NE 0．6cc）剂量仪（NE FARMER 2570）测量得到实际吸收剂量。结果：在细胞培养瓶中装满细胞培养液时模拟调强照射实测得到397cGy，与理论值相差-0．8％；在细胞培养瓶中不装细胞培养液时模拟调强照射实测得到395cGy，与理论值相差-1.3％。结论：用CT模拟定位，用计划系统通过设野中野的方法设计模拟调强照射计划是可行的，可以实现模拟调强照射离体细胞，理论剂量与实测剂量相差小于2％。     

不同剂量X射线对人外周血有核细胞DNA及精子DNA损伤的比较

目的:应用单细胞凝胶电泳技术检测不同剂量X射线对人离体外周血有核细胞DNA及精子DNA的损伤,评估外周血有核细胞及精子在高剂量X射线照射后DNA的损伤程度.方法:采用血常规正常的人外周血和采集精液常规正常的人精液,用能量为6MV的X射线给予0Gy,2Gy,4Gy,6Gy,8Gy,10Gy的剂量照射.照射后1h内进行单细...     

JAK-STAT信号通路、IL-1β和IL-6在X射线辐照诱导PC12细胞损伤中的调控作用

目的:探究JAK-STAT信号通路及炎症因子IL-1β、IL-6是否参与X射线诱导的PC12细胞辐射损伤。方法:采用X射线分别以2、4和8 Gy剂量照射PC12细胞,照射后24 h通过酶联免疫法检测IL-1β和IL-6的表达水平;Western blot检测p-JAK1、p-JAK2、p-STAT1、p-STAT3和p-STAT5的蛋白水平。结果:与正常对照组相比,细胞经不同剂量X射线照射24 h后,IL-1β和IL-6的表达水平均升高,且与辐照剂量呈剂量依赖性;p-JAK1、pJAK2、p-STAT1、p-STAT3和p-STAT5的蛋白水平均升高,且上调程度与辐照剂量呈剂量依赖性。结论:JAK-STAT信号通路、IL-1β和IL-6可能参与X射线照射诱导PC12细胞的损伤调控。     

原发性小肝癌的立体定向放射治疗计划设计

目的:探讨原发性小肝癌γ射线立体定向放射治疗计划的设计。方法:2008.05～2010.12采用γ射线立体定向放射治疗26例原发性小肝癌患者,29个计划靶区体积(Vptv)均≤100 cm3,PTV周边照射总剂量4000 cGy～5400 cGy,分割处方剂量400 cGy～600 cGy,每日治疗,6次/周。分析各立体定向放射治疗计划。结果:PTV均由70%～90%等剂量线包绕,每一计划至多需3个等中心。靶区剂量均匀指数1.06～1.43,没有正常组织受照剂量超过相应的耐受剂量。结论:能设计出优秀的原发性小肝癌的立体定向放射治疗计划,治疗计划所需等中心数少,靶区剂量均匀。     

X射线照射对Hep-2细胞吸收光谱的影响

本文采用分光光度法研究了不同剂节X射线照射人上皮样喉癌细胞株（Hep-2）后对其吸收光谱的影响。旨在能为临床X射线放射治疗喉癌提供最佳剂量的参考。通过对六个剂节组与空白对照组吸收光谱的研究，发现不同剂量组的Hep-2细胞内蛋白质及核酸所受伤害与修复的程度不同，且发现癌细胞所受照射的剂量与其生长所受抑制程度、吸收光谱之间有一定的联系。为下一步用光谱技术的研究喉癌X射线放射最佳剂量的问题奠定了基础。     

高能X射线肿瘤照射靶区的生物学位置的实验模拟研究

目的:研究50MV高能X射线照射患者时光核反应产生的正电子发射核<'11>C、<'15>O在PET的显象技术及信息,探讨用该信息定量研究照射的肿瘤生物靶区准确度和剂量分布情况.方法:50 MV的X射线照射圆柱体模后快速置于PET上扫描显像和数据处理,确定射野轨迹和照射区大小并与物理射野大小比较,确定<'11>C活度分布...     

光子辐射输运中次级效应对辐射剂量深度分布的影响

目的:模拟光子输运的过程,记录各相互作用和次级粒子对剂量计算的贡献,总结分析其对剂量贡献的大小.方法:PENELOPE程序包提供了模拟光子和电子输运的基本MC模块.基于所关心的物理问题本文对PENELOPE程序包进行二次编程,以在模拟过程中追踪光子输运详细过程,记录各相互作用及次级粒子对剂量的贡献.结果:首先研究在相同照射条件下,4种能量(10 keV,100keV,1 MeV,10MeV)的光子产生的中心轴剂量分布,次级粒子的软碰撞和硬碰撞产生的中心轴剂量分布,以及各级次级粒子的中心轴剂量分布;然后研究在相同照射条件下,4种能量(30keV,40keV,50keV,60keV)的光子产生的次级康普顿效应和次级光电效应对中心轴剂量分布.结论:不同能量下,次级电子软碰撞对于中心轴剂量的贡献起主要作用,次级光电效应对中心轴剂量的贡献随能量的增加而减小,而第一代次级粒子对于中心轴剂量的贡献大于其它代粒子的贡献.     

术中放疗深度剂量、表面剂量及漏射线的剂量研究

目的：研究术中放疗深度剂量、表面剂量及漏射线的剂量的测量方法，总结临床应用经验。方法：使用IC-15电离室和WEUHOFER WP700蓝水箱测量加速器电子束术中放疗限光筒中心轴百分深度剂量和表面剂量：采用Farmer剂量仪2570及有机玻璃小水箱，测量剂量输出因子及限光筒外漏射线。结果：6MeV和9MeV表面剂量分别为85．9％、87．2％。12MeV、16MeV、20MeV限光筒外1cm处漏射线分别达到6．81％、6．10％、6．85％。结论：术中放疗是一种复杂的治疗技术，在临床辐射剂量学上有其独特性。术中放疗表面剂量应该满足90％，建议增加填充物，如盐水纱布等，提高表面剂量。限光筒外的泄漏射线必须小于中心轴最大剂量的5％，做好肿瘤周围正常组织的辐射防护很重要。     

Monte Carlo simulation on a gold nanoparticle irradiated by electron beams

This study investigated the secondary electron production from a gold nanoparticle (GNP) irradiated by monoenergetic electron beams using Monte Carlo (MC) simulation. Spherical GNPs with diameters of 2, 50 and 100 nm in water were irradiated by monoenergetic electron beams with energies equal to 50 keV, 250 keV, 1 MeV and 4 MeV. MC simulations were performed using the Geant4 toolkit to determine the energy of the secondary electrons emitted from the GNPs. The mean effective range and deflection angle of the secondary electrons were tracked. Energy depositions inside and outside the nanoparticles due to the secondary electrons were also calculated. For comparisons, simulations were repeated by replacing the GNPs with water. Our results show that the mean effective range of secondary electrons increased with an increase of the GNP size and electron beam energy. For the electron beam energy and GNP size used in this study, the mean effective range was 0.5-15 μm outside the nanoparticle, which is approximately within the dimension of a living cell. The mean deflection angles varied from 78 to 83 degrees as per our MC results. The proportion of energy deposition inside the GNP versus that outside increased with the GNP size. This is different from the results obtained from a previous study using photon beams. The secondary electron energy deposition ratio (energy deposition for GNP/energy deposition for water) was found to be highest for the smallest GNP of 2 nm diameter in this study. For the energy deposited by the secondary electron, we concluded that the addition of GNPs can increase the secondary electron energy deposition in water, though most of the energy was self-absorbed by the large nanoparticles (50 and 100 nm). In addition, an electron source in the presence of GNPs does not seem to be better than photons as the yield of secondary electrons per unit mass of gold is less than water.     

儿童T淋巴细胞不同剂量辐射后DNA合成的增殖反应的应答

观察儿童T淋巴细胞低剂量辐射后DNA合成的刺激效应和对大剂量辐射的适应性反应。 8例儿童外周血T淋巴细胞培养后 ,予以不同的低剂量辐射 ,用14 C TdR (14 C 胸腺嘧啶核苷 )或3 H TdR (3 H 胸腺嘧啶核苷 )掺入法观察T淋巴细胞DNA合成 ,用掺入百分率和辐射损伤减轻百分数 (DRP )分别表达刺激效应和适应性反应。T淋巴细胞经 2、 5、 10cGy照射后14 C TdR掺入与 0cGy比较分别是 10 7 7%、 12 5 5 %、 133 8% ,明显增加了DNA合成。分别予以 0 5、 1 0、 1 5、 2 0、 3 0、 4 0cGy不同剂量辐射后 ,DRP分别是 2 0 8%、 33 2 %、 5 3 4 %、 4 9 0 %、 2 8 9%。 1 5cGy辐射后 6、 2 4、 4 8、 72h ,DRP分别是2 2 2 %、 5 3 4 %、 36 6 %、 11 1%。 1 5cGy辐射后 2 4h再予以 1、 3、 5、 7Gy不同大剂量辐射 ,DRP分别是 30 7%、 4 5 1%、2 6 4 %、 11 9%。儿童T淋巴细胞经适宜的低剂量辐射后可以明显增加DNA合成 ,1 5cGy辐射后 2 4h对 3Gy大剂量辐射适应性反应表达最为充分     

IL-11 synergizes with IL-3 in promoting the recovery of the immune system after irradiation

In our previous studies aiming at the design of appropriateto accelerate the recovery of the system after irradiation wefound that recombinant murine (rmu) It-3 treatment induc3esdifferentiation and growth of thymocytes and splenic T and Blymphocytes in mice exposed to X-rays(200-500 cGy). These studieswere extended to investigate the effectss of recombinant human(rhu)IL-11. Results indicate that rhuIL-11 is able to restorethymus and spleen cell numbers as well as T and B cell mitoticresponsiveness in mice exposed to 200 cGy but not to 300cGy. However, recovery, of thymus and spfeen cell numbers and functionscould be accelerated also in mice exposed to higherr doses itrhyuIL-11 was given with rmuIL-3. Recovery was complete assoon as 7 daysafter irradiation. A large doss range of bothcytokines was explored and the synergiatic effect of the twocytokines was evident when a relatively small dose of rhyuIL-11was injected with graded doses of rmuIL-3. The recovery ofthe immune system in irradiated mice injected with these cytokineswas independent from Bcl-2 expression, suggesting that elliminationofdamaged cells by apoptosis is uneffected by hamatopoistic cytokines.     

The use of trans-vinylene formation in quantifying the spatial distribution of electron beam penetration in polyethylene. Single-sided,double-sided and shielded irradiation

The use of the quantification of trans-vinylene unsaturations in irradiated ultrahigh molecular weight polyethylene (UHMWPE) in determining the spatial distribution of electron beam penetration was investigated. UHMWPE was irradiated with a 10MeV linear electron beam accelerator to 100kGy at both room temperature and 125 degrees C in air. The irradiation was carried out in shielded and unshielded single-sided and unshielded double-sided irradiation modes. Dose-depth profiles were measured by quantifying the yields of trans-vinylene unsaturations as a function of depth away from the e-beam incidence surfaces using infrared spectroscopy. The extent of beam penetration increased with increasing irradiation temperature as was manifested by the increase in the iso-dose penetration with the unshielded single-sided irradiation and increased dose overlap with the unshielded double-sided irradiation. The optimum thickness with maximum uniformity in dose-depth distribution for double-sided irradiation was 85 and 90mm for 25 degrees C and 125 degrees C irradiation temperatures, respectively.     

Therapeutic doses of radiation alter proliferation and attachment of osteoblasts to implant surfaces

Osseointegration of implants in irradiated bone is inadequate. The effect of radiation on cell-implant material interaction has not been adequately studied. The goal of this study was to investigate the effects of ionizing radiationon the proliferation, differentiation, and attachment of osteoblasts to commercially pure titanium (cpTi). Human fetal osteoblasts (hFOB) were irradiated either before or after plating in tissue culture (TC) dishes with or without cpTi disks. Radiation was single dose of 10 cGy, 25 cGy, 50 cGy, 1 Gy, 2 Gy, 4 Gy or 8 Gy. Cell proliferation was determined by counting trypsinized cells on 7 days after irradiation. Attachment of irradiated hFOB was measured indirectly by counting cells 2 and 6 h after plating. Differentiation was evaluated by alkaline phosphatase activity. Compared with nonirradiated sham controls, higher doses of radiation significantly reduced cell attachment and proliferation. Both proliferation and attachment were significantly lower on cpTi compared with TC. Attachment decreased based on the length of postirradiation period. Although differentiation was significantly enhanced by a dose of 8 Gy, proliferation was lowest. These initial studies show that effects of therapeutic doses of radiation on osteoblasts varied depending on the surface, time-elapsed, and amount of radiation.     

Apoptosis induced by generated OH radicals inside cells after irradiation

OH radicals play a major role in radiation-induced DNA and cell membrane damage. These types of damage can also induce death by apoptosis through activation of a pro-apoptosis pathway. We attempted to detect OH radicals inside human promyelocytic leukemia (HL60) cells and estimate the relationship between radiation-induced apoptosis and OH radicals generated inside the cells. Electron spin resonance spectroscopy showed that OH radicals were generated by X-rays within irradiated cell pellets and the relative signal intensities of OH radicals increased with the radiation dose. Agarose gel electrophoresis revealed that the death of HL60 cells by apoptosis was accompanied by internucleosomal DNA fragmentation at 2 h after irradiation with 10-30 Gy. On ultrastructure evaluation by transmission electron microscopy, certain irradiated HL60 cells demonstrated condensed chromatin forms at the nuclear membrane and nuclear fragmentation. The frequency of apoptotic cells with condensation and fragmentation of nuclear chromatin increased with radiation dose in semithin sections. The increase of quantitative DNA fragmentation and percentage of non-living cells also correlated with radiation dose. These results suggest that OH radicals are generated inside cells before apoptosis occurs. The amount of OH radicals generated correlates with apoptotic cell death.     

高能电子线放射治疗的剂量学参数测量与分析

目的：对高能电子线总输出因子、百分深度剂量、深度剂量分布的剂量学参数进行测量并分析讨论。方法：在Varian23EX直线加速器上,利用9606剂量测量仪和0．6cc指型电离室测量不同能量、不同限光筒及不同射野下的输出剂量并作归一,得到我们所要的剂量学参数,然后分析数据。结果：总输出因子在不同能量下与正方形射野边长的关系可满足等式：y=a·e^bx＋c·e^dx。水模体百分剂量分布中,6MeV电子线各限光筒的90％、85％等剂量深度基本不变,9MeV-15MeV下90％、85％等剂量深度随着限光筒尺寸增大而变深。对于水模体的深度剂量分布情况,6MeV和12MeV能量的10cmx10cm、15cmxl5cm限光筒均整区内对称点的最大相对剂量差分别都为0．04％、O．03％。结论：通过测量掌握实际照射中的剂量学特点．对于电子线剂量的准确计算以及临床计划制定具有很大的参考价值。     

Early experience in using and 18 Me V linear accelerator for mycosis fungoides at Howard University Hospital.

This paper describes the problems and solutions in using 18 MeV linear accelerator, with minimum 6 MeV electron capability, for total skin irradiation for mycosis fungoides. The 6 MeV electron energy can be degraded to acceptable electron energy of 3.2 MeV by interposing a plexiglass sheet of 9.6 mm in the beam. To minimize the bremsstrahlung, the degrading plexiglass should be kept away from the machine head. A wide area with uniform dose distribution over single plane can be achieved by using dual fields but homogenous dose distribution over irregular body surface cannot be achieved mainly because of self-shielding. The nails and the ocular lens can be easily shielded from the low energy electrons with 1.5 mm lead shield.     

Radio-physical properties of micelle leucodye 3D integrating gel dosimeters

Recently, novel radiochromic leucodye micelle hydrogel dosimeters were introduced in the literature. In these studies, gel measured electron depth dose profiles were compared with ion chamber depth dose data, from which it was concluded that leucocrystal violet-type dosimeters were independent of dose rate. Similar conclusions were drawn for leucomalachite green-type dosimeters, only after pre-irradiating the samples to a homogeneous radiation dose. However, in our extensive study of the radio-physical properties of leucocrystal violet- and leucomalachite green-type dosimeters, a significant dose rate dependence was found. For a dose rate variation between 50 and 400 cGy min(-1), a maximum difference of 75% was found in optical dose sensitivity for the leucomalachite green-type dosimeter. Furthermore, the measured optical dose sensitivity of the leucomalachite green-type dosimeter was four times lower than the value previously reported in the literature. For the leucocrystal violet-type dosimeter, a maximum difference in optical dose sensitivity of 55% was found between 50 and 400 cGy min(-1). A modified composition of the leucomalachite green-type dosimeter is proposed. This dosimeter is composed of gelatin, sodium dodecyl sulfate, chloroform, trichloroacetic acid and leucomalachite green. The optical dose sensitivity amounted to 4.375 × 10(-5) cm(-1) cGy(-1) (dose rate 400 cGy min(-1)). No energy dependence for photon energies between 6 and 18 MV was found. No temperature dependence during readout was found notwithstanding a temperature dependence during irradiation of 1.90 cGy °C(-1) increase on a total dose of 100 cGy. The novel gel dosimeter formulation exhibits an improved spatial stability (2.45 × 10(-7) cm(2) s(-1) (= 0.088 mm(2) h(-1))) and good water/soft tissue equivalence. Nevertheless, the novel formulation was also found to have a significant, albeit reduced, dose rate dependence, as a maximum difference of 33% was found in optical dose sensitivity when the dose rate varied between 50 and 400 cGy min(-1). By pre-irradiating the novel leucomalachite green-type dosimeter to 500 cGy, the apparent difference in dose response between 200 and 400 cGy min(-1) was eliminated, similar to earlier findings. However, a dose response difference of 38% between 50 and 200 cGy min(-1) was still measured. On the basis of these experimental results it is concluded that the leucodye micelle gel dosimeter is not yet optimal for dose verifications of high precision radiation therapy treatments. This study, however, indicates that the dose rate dependence has a potential for improvement. Future research is necessary to further minimize the dose rate dependence through extensive chemical analysis and optimization of the gel formulation. Some insights into the physicochemical mechanisms were obtained and are discussed in this paper.