17β-雌二醇对破骨细胞骨架和骨吸收功能影响的实验研究

目的　研究17β-雌二醇对体外培养破骨细胞细胞骨架的影响,以及这种影响与骨吸收功能之间的关系。方法　在破骨细胞培养液中加入不同浓度的17β-雌二醇,用F-actin特异性抗体进行免疫荧光染色,激光共聚焦显微镜观察破骨细胞细胞骨架的变化情况,同时用扫描电镜观察破骨细胞在骨片形成骨吸收陷窝数目及面积的变化。结果　随着17β-雌二醇浓度的升高,实验组破骨细胞F-actin相对荧光强度从(89 6±7 5)%下降至(34 7±5 4)% (与对照组荧光强度相比),细胞内微丝收缩变短,排列紊乱,细胞波状缘消失,破骨细胞伸展面积从(1289±53)μm2 /细胞核下降至(406±42)μm2 /细胞核,同时,骨吸收陷窝的数目和面积从(131 5 ±11 7)个/片和(2157±51)μm2 减少到(16 8±4 0 )个/片和(965±75)μm2。生理浓度(10-7mol/l)及其以上17β-雌二醇处理组与对照组比较,差异有显著性(P<0 01 )。结论　17β-雌二醇影响破骨细胞内细胞骨架的结构,下调F-actin的表达,降低破骨细胞的活动能力,从而抑制破骨细胞的骨吸收功能。     

17β-雌二醇调控子宫内膜癌细胞孤儿核受体ERRα表达的研究

背景与目的:雌激素受体相关受体α(estrogenreceptor-relatedreceptorα,ERRα)是孤儿核受体亚家族成员之一,可与雌激素受体α(estrogenreceptorα,ERα)竞争结合同一靶基因位点,从而干扰雌激素-雌激素受体核内信号通路的转导,因而可能在子宫内膜癌的发生方面发挥一定作用。本研究旨在探讨17β-雌二醇(E2)对子宫内膜癌细胞孤儿核受体ERRα的调控作用,明确ERRα在子宫内膜癌发生中的作用及与ER信号通路的关系。方法:采用RT-PCR和Westernblot方法,检测不同浓度17β-E(210-10、10-8、10-6mol/L)作用于ERα阳性的子宫内膜癌细胞系Ishikawa细胞和ERα阴性的子宫内膜癌细胞系HEC-IA细胞24h、48h后ERRαmRNA水平和蛋白水平的变化,并应用完全性ER拮抗剂ICI182780同时作用细胞,观察是否可阻断E2对ERRα的调控作用。结果:不同浓度的17β-E2作用于Ishikawa细胞24h、48h后ERRαmRNA水平及蛋白水平均有不同程度的下调,以10-8mol/L作用后下调最明显。同时加入10-8mol/LE2和10-6mol/LICI182780作用于Ishikawa细胞后,E2对ERRα的下调作用被阻断。不同浓度的17β-E2作用于HEC-IA细胞24h后ERRαmRNA水平出现不同程度上调,但蛋白水平未见明显变化。当17β-E2作用细胞48h后,ERRα蛋白水平出现明显上调,以10-8mol/L作用后上调最明显。同时加入10-8mol/LE2和10-6mol/LICI182780作用于HEC-IA细胞后,E2对ERRα的上调作用无明显变化。结论:17β-E2可下调Ishikawa细胞ERRα的表达,且这种降调作用是通过ER介导完成的;17β-E2可上调HEC-IA细胞ERRα的表达,且这种上调作用不被完全性ER拮抗剂ICI182780所阻断。     

β-榄香烯对小鼠B16黑色素瘤细胞粘附、运动和间隙连接通讯功能的影响

目的：探讨β揽香烯对小鼠Ｂ１６黑色素瘤细胞粘附和运动能力的影响。方法：采用细胞培养、电镜及划痕染料示踪技术,研究了β榄香烯对小鼠Ｂ１６黑色素瘤细胞粘附与运动能力、间隙连接结构及其间隙连接通讯功能的影响。结果：２０～４０μｇ／ｍｌ的β榄香烯可显著抑制Ｂ１６细胞对纤维结合蛋白和层粘连蛋白两种基质的粘附,抑制Ｂ１６细胞的运动,延迟吸管尖部所致细胞单层损伤的愈合。结论：提示β榄香烯对Ｂ１６细胞粘附和运动能力的抑制可能是其抗肿瘤转移作用的机制之一。     

18F-FES在乳腺癌患者体内摄取与病理免疫组化的关系

背景与目的：16α-¹⁸F-17β-雌二醇(¹⁸F-FES)作为雌激素受体(estrogen receptor, ER)特异性显像剂,可在活体内反映ER的表达状况。本研究主要探讨乳腺癌患者体内¹⁸F-FES摄取结果与病理免疫组化的相关性。方法：自行制备¹⁸F-FES,入组26例乳腺癌患者(17例原发性乳腺癌,9例复发转移性乳腺癌),分别进行¹⁸F-FES及¹⁸F-FDG PET/CT显像,对每例患者进行空心针穿刺或手术治疗,对比相应病灶的免疫组化和¹⁸F-FES、¹⁸F-FDG摄取结果。结果：96.15%(25/26)的患者¹⁸F-FES结果与ER病理免疫组化一致,以¹⁸F-FES SUV_max≥1.5为ER阳性,¹⁸F-FES PET/CT显像诊断乳腺癌病灶ER阳性的灵敏度为93.33%,特异度为100%。ER、PR的免疫组化结果与¹⁸F-FES的SUV_max呈明显的正相关;HER-2/Neu的免疫组化结果与¹⁸F-FES的SUV_max呈负相关。结论：¹⁸F-FES有望用于全面反映乳腺癌患者全身病灶的ER表达情况,为临床个体化治疗方案的制定提供帮助。     

Electron dosimetry of irregular fields on the Clinac 18.

A technique has been devised for obtaining irregularly shaped fields for electron beam therapy on a Clinac 18 Linear Accelerator. This technique utilizes low melting point alloy cutouts (“Ostalloy”, manufactured by Arconium Corporation of America, Providence, RI 02909, U.S.A., containing 50% bismuth, 26.7% lead, 13.3% tin and 10% cadmium), which fit inside the standard Varian cones. Studies have shown that this method of field shaping does not adversely affect either the field flatness or the percent depth dose distributions. The dosimetry for these irregular fields has been investigated extensively. It has been found that the equivalent area technique generally used in X-ray treatments can be utilized reasonably well to predict the dose for shaped electron fields. Clinical experience with this system over the past year indicates that the setup for initial simulation and subsequent treatments is straightforward, and the time required minimal.     

关于电子荧光类射野影像系统作为出射剂量仪使用的研究

目的研究利用射野影像系统进行出射剂量测量的可能性。以便能进一步把该类系统发展为剂量仪系统。材料与方法使用荧光型电子射野影像系统，探头由金属板—荧光屏和Ｐｌｕｍｂｉｃｏｎ照像机组成。通过与电离室及射野证实片所测结果的比较，建立一套与像素位置对应的灰度校正矩阵。并在多种射野面积和体模厚度下验证，所用射线为６ＭＶ－Ｘ线。结果通过对该系统的各种性能测试，如灰度的稳定性、探头的均匀性、剂量响应曲线、灰度的射野依赖性及对体模厚度的依赖性，发现短期稳定性好于１％，有较明显的灰度饱和性，但需作灰度饱和校正。作为相对剂量仪使用时，只要建立一个探头非均匀性校正矩阵，就能与证实片的剂量结果保持一致，误差小于±５％。结论研究证明，电子射野影像系统完全可以成为一套剂量仪系统。在对靶区的位置进行实时监测的同时，还能通过对影像灰度的计算，得出出射野的剂量分布     

Image registration of BANG gel dose maps for quantitative dosimetry verification

Background: The BANG® (product symbol SGEL, MGS Research Inc., Guilford, CT) polymer gel has been shown to be a valuable dosimeter for determining three-dimensional (3D) dose distributions. Because the proton relaxation rate (R2) of the gel changes as a function of absorbed dose, MR scans of the irradiated gel can be used to generate 3D dose maps. Previous work with the gel, however, has not relied on precise localization of the measured dose distribution. This has limited its quantitative use, as no precise correlation exists with the planned distribution. This paper reports on a technique for providing this correlation, thus providing a quality assurance tool that includes all of the steps of imaging, treatment planning, dose calculation, and treatment localization.

Methods and Materials: The BANG® gel formulation was prepared and poured into spherical flasks (15.3-cm inner diameter). A stereotactic head ring was attached to each flask. Three magnetic resonance imaging (MRI) and computed tomography (CT) compatible fiducial markers were placed on the flask, thus defining the central axial plane. A high-resolution CT scan was obtained of each flask. These images were transferred to a radiosurgery treatment-planning program, where treatment plans were developed. The gels were irradiated using our systems for stereotactic radiosurgery or fractionated stereotactic radiotherapy. The gels were MR imaged, and a relative 3D dose map was created from an R2 map of these images. The dose maps were transferred to an image-correlation program, and then fused to the treatment-planning CT scan through a rigid body match of the MRI/CT-compatible fiducial markers. The fused dose maps were imported into the treatment-planning system for quantitative comparison with the calculated treatment plans.

Results: Calculated and measured isodose surfaces agreed to within 2 mm at the worst points within the in-plane dose distributions. This agreement is excellent, considering that the pixel resolution of the MRI dose maps is 1.56 × 1.56 mm, and the treatment-planning dose distributions were calculated on a 1-mm dose grid. All points within the dose distribution were well within the tolerances set forth for commissioning and quality assurance of stereotactic treatment-planning systems. Moreover, the quantitative evaluation presented here tests the accuracy of the entire treatment-planning and delivery process, including stereotactic frame rigidity, CT localization, CT/MR correlation, dose calculation, and radiation delivery.

Conclusion: BANG® polymer gel dosimetry coupled with image correlation provides quantitative verification of the accuracy of 3D dose distributions. Such quantitative evaluation is imperative to ensure the high quality of the 3D dose distributions generated and delivered by stereotactic and other conformal irradiation systems.     

~(11)C-鬼臼毒素和~(18)F-脱氧葡萄糖示踪剂在小鼠肺癌模型PET影像学检查中的应用

目的 对比~(11)C-鬼臼毒素(PDT)和~(18)F-脱氧葡萄糖(FDG)在荷肺腺癌小鼠体内的生物学分布及在PET中的显像,评价_(11)C-PDT作为新型示踪剂在肺癌显像中的作用.方法 24只荷肺腺癌小鼠随机分为2组,每组12只,分别经尾静脉注入~(11)C-PDT和~(18)F-FDG,于注药60 min后用井型探测仪测量~(11)C-PDT和~(18)F-FDG在小鼠各脏器内的生物学分布,并行 PET 显像.结果 ~(11)C-PDT和~(18)F-FDG在肿瘤组织中均有较高的放射性摄取,但是~(11)C-PDT组肿瘤组织的放射性摄取值[(0.65±0.20)%ID/g]明显低于~(18)F-FDG组[(7.44±1.56)%ID/g,P<0.01].~(11)C-PDT组放射性摄取最高的部位依次为肝、肾和血液,而~(18)F-FDG组放射性摄取最高的部位依次为心脏、肿瘤和肾.~(11)C-PDT组中,肿瘤组织对肌肉组织的T/NT值相对较高,达2.02±0.56,但仍低于~(18)F-FDG组(2.95±0.49,P<0.01).~(11)C-PDT组中,肿瘤组织对其他脏器的T/NT值均<2.~(11)C-PDT组荷肺腺癌小鼠PET显像可见腹腔脏器及肿瘤部位有放射性热区,~(18)F-FDG组可见心脏、肿瘤及腹腔脏器放射性浓聚明显,两种示踪剂的肿瘤显像均较清晰.结论 ~(11)C-PDT在肺癌组织中的摄取高于肌肉组织,通过PET显像可以显示肺部肿瘤.~(11)C-PDT可以作为肺癌显像的示踪剂.     

Radiation dosimetry of <Superscript>131</Superscript>I-chlorotoxin for targeted radiotherapy in glioma-bearing mice

Chlorotoxin, or TM-601, is a peptide derived from the venom of the scorpionLeiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal tissues. Targeted radiotherapy using ¹³¹I-Chlorotoxin is promising for post-surgery treatment of brain tumors. This study reports dosimetry results of ¹³¹I-Chlorotoxin in athymic nude mice with intracranially implanted human glioma xenografts and projected radiation doses in patients receiving 370 MBq of ¹³¹I-Chlorotoxin. ¹²⁵I/¹³¹I-Chlorotoxin were injected into the right brain where D54 MG xenografts were implanted. Mice were sacrificed 24–96 h later. The blood, normal organs, and tumors were weighed and counted to determine ¹³¹I-Chlorotoxin concentration. The radiation dose from ¹³¹I was calculated based on non-penetrating radiation in the mouse model. Assuming similar tissue uptake in mice and patients, radiation doses for patients were extrapolated. Distributions of ¹²⁵I/¹³¹I-Chlorotoxin were only significant in tumor, stomach, kidneys, and brain (injection site), reflecting non-specific uptake of Chlorotoxin in normal tissues. Mean radiation dose (cGy/37kBq) was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach, 16.0 for kidneys in mice. For intracranial injection of 370MBq ¹³¹I-Chlorotoxin in patients, extrapolated patient dose (cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys, 227 to tumor, suggesting that 3.7GBq of ¹³¹I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.     

The impact of PET and SPECT on dosimetry for targeted radionuclide therapy

Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however are that--some of the positron emitting isotopes have a shorter half-life--non-standard quantification procedures have to be performed--the availability of the radiopharmaceutical is presently limited; Many 3D-tools and -techniques are now available to the physicist and clinician to enable absorbed dose calculations to both target and critical organs-at-risk. The challenge now facing nuclear medicine is to enable this methodology to be routinely available to the clinic, to ensure common standard operating procedures between centres and in particular to correlate response criteria with absorbed dose estimates.     

ORIGINAL ARTICLE: Pilot comparison of 18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT with conventional imaging in prostate cancer

Introduction: Conventional imaging (CI) is known to have limitations with respect to staging of patients with primary or relapsed prostate cancer. Positron emission tomography/computed tomography (PET/CT) with ¹⁸F-flurodeoxyglucose (FDG) is also often suboptimal because of low tracer avidity, but ¹⁸F-fluorocholine (FCH) appears to be a promising alternative molecular imaging probe. We report a prospective pilot study of PET/CT comparing both tracers for staging and restaging of patients with prostate cancer. Methods: Sixteen prostate cancer patients were evaluated (7 for staging and 9 for restaging). All patients also underwent CI, comprising at least an abdominopelvic CT and a bone scan. All imaging results and other relevant data were extracted from the imaging reports and medical charts. Results: Based on all imaging-detected disease sites, both FCH-PET/CT and FDG-PET/CT (79%) were more sensitive than CI (14%), with the highest number of sites of nodal and distant disease on FCH PET/CT. FCH-PET/CT alone would have provided sufficient clinical information to form an appropriate management plan in 88% of cases, as compared with 56% for CI. Conclusion: FCH-PET/CT has the potential to impact on the management of patients with prostate cancer significantly more often than CI.     

移动条野技术的放射生物学和剂量学基础及改进

目的：阐明常规移动条独特的优点及其局限性，并对其进行改进。方法：从放射生物学方面包括时间剂量因子、分次剂量因子和体积剂量因子等三个方面及从剂量学方面分析了移动条野照射技术，针对其局限笥，引进了由靶区长度每次剂量，总剂量和疗程时间决定的照射野宽度与每次铥距离的计算模型。结果：移动条野照射技术在一定条件下能提高肿瘤的生物效应，同时减少正常组织的反应。结论：移动条野照射技术有其本身的适应证和应用价值。