抗人肝癌188Re-免疫磁性纳米微粒的生物学分布和肿瘤细胞抑制实验

目的探讨抗人肝癌188Re-免疫(Hepama-1)磁性纳米微粒免疫学活性、体内生物学分布、肝靶向性及抑瘤作用。方法对比188ReO4-、188Re-Hepama-1、188Re-磁性纳米微粒,研究尾静脉注射188Re-免疫磁性纳米微粒后4h、24h在昆明小鼠体内的分布情况;在肝区外加磁场及无磁场状态下,研究新西兰大白兔体内的肝磁靶向性;采用溴化四甲基唑法,研究4种188Re标记物对肝癌细胞株SMMC-7721的抑制效果。结果188Re-免疫磁性纳米微粒在肝内摄取量最大;在磁区肝组织放射活性较非磁区肝组织明显增加,二者的放射活性比值为1.87;对肝癌细胞株SMMC-7721半数抑制放射性活度仅为188ReO4-的1/4左右。结论188Re-磁性纳米微粒具有良好的磁感应性能、免疫活性及明显的肝靶向性。     

188Re标记免疫靶向磁性纳米微粒及其生物学分布

目的研究^188Re标记具有HER-2／neu癌基因靶向特异性的Herceptin免疫磁性纳米微粒及其在小鼠体内的生物学分布。方法利用戊二醛作为交联剂，将人源性单克隆抗体Herceptin与化学修饰的磁性纳米微粒进行连接，构建免疫磁性纳米微粒。采用直接标记法将^188Re标记到免疫磁性纳米微粒上。采用羰基铼标记法，以fac-[^188Re（CO）3（H2O）3]^＋作为放射性标记前体，对表面固载组氨酸的磁性纳米微粒进行标记。分别测定所制备^188Re标记物的标记率和体外稳定性及免疫磁性纳米微粒的单克隆抗体免疫活性，并观察^188Re标记的磁性纳米微粒及免疫磁性纳米微粒的小鼠体内生物分布。结果经扫描电镜证实免疫磁性纳米微粒的单个粒径大小平均为60nm，而表面固载组氨酸的磁性纳米微粒的粒径平均为30nm。^188Re对Herceptin、免疫磁性纳米微粒及固载组氨酸的磁性纳米微粒的标记率均〉90％，在小牛血清中具有良好的体外稳定性，并且磁性纳米微粒上连接的单克隆抗体仍保持较高的免疫活性。小鼠体内分布实验显示^188Re标记的磁性纳米微粒及免疫磁性纳米微粒在血液中有较高的放射性分布且血循环时间较长，同时两者在肝内均有较多的摄取。结论^188Re标记的磁性纳米微粒及免疫磁性纳米微粒在体外及动物体内较稳定，无明显的^188Re脱落。可用于下一步荷瘤裸鼠体内的研究。     

载药磁性纳米微粒靶向治疗肿瘤研究进展

载药磁性纳米微粒是将药物、生物活性物质或治疗用放射性核素等包裹于磁性纳米微粒内或吸附、连接于磁性纳米微粒表面，或混合、溶解于材料基质中而构成，其大小为纳米级。在足够强的外加磁场作用下，其在体内定向移动、定向浓集，从而达到提高治疗效果、降低毒副作用的目的。     

188Re-Herceptin-磁性纳米微粒的体外抗肿瘤作用

目的探讨^188Re—Herceptin-磁性纳米微粒在外置磁场下对HER-2／neu癌基因高表达的SKBR-3乳腺癌细胞的靶向结合性及抗癌作用。方法采用戊二醛交联法使人源性单克隆抗体Her—ceptin与磁性纳米微粒交联，用直接标记法制备^188Re—Herceptin及^188Re—Herceptin-磁性纳米微粒，用羰基铼标记法制备^188Re-磁性纳米微粒。肿瘤细胞体外抑制实验设4个组：^188Re—Herceptin-磁性纳米微粒组、^188Re—Herceptin组、^188Re-磁性纳米微粒组和^188ReO4^-组，各组均设3．7×10^4、18．5×10^4、37×10^4、55．5×10^4、74×10^4Bq／ml5个放射性剂量级别；另设生理盐水对照组。采用四甲基偶氮唑蓝（MTT）法测定各组的抑瘤效应，计算相对抑制率，采用半数抑制放射性浓度（IC50）对各组抑瘤作用进行比较和评价。结果^188Re—Herceptin-磁性纳米微粒和^188Re—Herceptin组对SKBR-3细胞均有较强杀伤作用，且呈剂量依赖性；而^188Re-磁性纳米微粒和^188Re04组的杀伤作用较弱0188Re—Herceptin-磁性纳米微粒组的IC50（53．1×10^4Bq／L）明显低于^188Re—Herceptin组（76．1×10^4Bq／L）；^188Re一磁性纳米微粒组和^188ReO4组的IC50分别为169×10^4和175×10^4Bq／L，明显高于前2组。结论^188Re—Herceptin-磁性纳米微粒和^188Re—Herceptin均可明显抑制体外培养的SKBR-3乳腺癌细胞增殖，且前者的抑制作用较后者强。     

吸附99mTcO4-的铁碳复合磁性药物载体在体内靶向分布研究

目的:探索铁碳复合磁性载体吸附99mTcO4-开展肝脏靶向治疗的可行性.方法:12只新西兰白兔随机分为3组:99mTcO4-水溶液组、未加磁场99mTcO4-铁碳复合磁性载体组和外加磁场99mTcO4-铁碳复合磁性载体组.左肝动脉置管分别注射该组剂型后利用SPECT分别对每只兔的肝脏、肺脏及甲状腺部位设定ROI,测定其部位在各时间点ROI放射性计数,并进行组间比较.结果:铁碳复合磁性载体对99mTcO4-具有良好的吸附性.99mTcO4-标记铁碳复合磁性载体加脉冲磁场组,在各时间点肝脏放射性计数均较其余2组明显增高.结论:脉冲磁场作用下磁性载体在靶区器官浓度增高、停留时间延长,从而增加药物有效作用浓度及时间,同时可减少药物在非靶区组织分布,减少不良反应.     

超顺磁性纳米粒在靶向显像和药物释放中的应用

超顺磁性纳米微粒（superparamagnetic nanoparticles,NPs）是铁磁材料的一类。在没有外加磁场的情况下,由于每个原子保持其相对有序状态,在快速变换磁性状态的过程中没有剩磁,因此,整体的NPs的磁矩不会随着热能的变化自由波动;     

经动脉导管磁性微粒栓塞肿瘤的临床分析

目的探讨磁性微粒(Fe3O4)经动脉导管栓塞肿瘤机理与临床应用。方法采用Seld inger技术插管,用Fe3O4 5-Fu混悬药液栓塞94例肿瘤患者,其中5例肝癌栓塞后靶区外置磁场,15例栓后手术切除标本HE染色制片,25例栓塞1月后DSA复查,前后图像对照作统计学处理。结果病理提示肿瘤组织坏死彻底,栓塞前后DSA图像定量分析P值<0.05,临床观察栓后综合征明显下降。结论Fe3O4微粒是一种永久性栓塞颗粒,具有缓慢栓塞作用,对减少栓后临床并发症有一定作用。     

重要蚊媒黄病毒对IFN-α介导的信号转导通路的抑制作用

目的:比较并探讨日本脑炎病毒Beijing-1株和登革2型病毒43株对宿主细胞内IFN-α介导的信号转导通路抑制作用的机制.方法:采用含萤火虫荧光素酶(Luciferase,Luc)报告基因的重组载体pISRE-Luc,通过检测IFN刺激应答元件(IFN-stimulated response element, ISRE)活性对病毒感染细胞内IFN-α介导的JAK-STAT信号转导通路的抑制作用进行定量分析.利用间接免疫荧光法观察在IFN-α作用下病毒感染细胞内STAT1分子的分布情况.进一步采用Western印迹分别检测在这两种病毒感染状态下宿主细胞内STAT1、JAK1和TYK2的磷酸化水平.结果:感染日本脑炎病毒和登革病毒的细胞在IFN-α作用下,ISRE活性与对照组相比均显著下降,而且日本脑炎病毒对宿主细胞内ISRE活性的抑制程度明显强于登革病毒;进一步研究发现,日本脑炎病毒可通过抑制JAK1和TYK2两种激酶的活性,降低STAT1的磷酸化水平,阻碍STAT1的核转运;而登革病毒则只抑制TYK2激酶的活化,降低STAT1的磷酸化及核转运水平.结论:日本脑炎病毒和登革病毒可通过不同的作用机制抑制IFN-α介导的JAK-STAT信号转导通路.     

基于ST68微泡的磁靶向控释载体的制备及性能研究

目的 构建具有超声和磁场双重响应特性的磁性微泡.方法 采用声振空化法制备基于表面活性剂的微泡超声造影剂(ST68),用多元醇法制备表面带负电荷的磁性Fe3O4纳米粒子.以微泡为模板,通过静电吸引层层自组装的方法使聚乙烯亚胺和磁性Fe3O4纳米粒子在微泡表面交替沉积,制备磁性微泡.搭建体外超声造影装置,对比注入磁性微泡(3×108个/ml)前后装置中硅胶管的超声图像,并观察对硅胶管施加磁场后磁性微泡的运动情况.对比注入磁性微泡前后新西兰大白兔肾脏的超声图像,以评价磁性微泡的体内超声造影效果.结果 制得的Fe3O4纳米粒子表面带有稳定的负电荷(-24.6±6.7)mV,组装得到的磁性微泡中超过98％的微泡粒径小于8μm,满足对超声造影剂大小的基本要求.注入磁性微泡前,硅胶管无回声信号;注入磁性微泡后,硅胶管内呈实性回声;施加磁场后,磁性微泡向磁场方向定向迁移.兔体内超声造影结果示推注磁性微泡前,超声图像不能显示肾;推注后肾脏影清晰.结论 制备的磁性微泡磁靶向和超声造影效果良好,为进一步研究具有诊断和治疗双重作用的磁靶向微泡超声造影剂打下了基础.     

金合欢素对丝裂原蛋白激酶p38α活性抑制作用的研究

目的 探讨金合欢素对丝裂原蛋白激酶p38α(p38αMAPK)的抑制作用。方法 应用分子对接软件Autodock Vina将金合欢素与靶酶三维晶体结构1KV2的活性位点进行分子对接,而后利用脂多糖诱导的小鼠RAW 264.7细胞炎症模型验证金合欢素对p38αMAPK的抑制作用。结果 金合欢素可结合于1KV2的活性位点处而阻碍底物三磷腺苷的进入,对p38αMAPK的生物学功能产生抑制作用。与模型组相比,阳性对照药地塞米松和金合欢素不同浓度干预后可明显下调小鼠RAW 264.7细胞炎症模型细胞上清液中一氧化氮和肿瘤坏死因子-α水平(P<0.05)。结论 金合欢素可能是通过作用于p38αMAPK活性位点而发挥抗炎的药理活性。     

Performance changes of an Anger camera in magnetic fields up to 10 G

Magnetic fields much larger than the earth's magnetic field can exist many feet away from NMR units. Gamma camera manufacturers already shield photomultiplier tubes from the earth's magnetic field (approximately 0.5 G). The effects of larger magnetic fields on an Anger camera, were made in fields up to 10 G. Sensitivity and positional stability were studied as a function of gantry angle in a magnetic field. Scans of uniform and hot rod sections of and ECT phantom were also performed. No visible artifacts were found in reconstructions of the phantom measured in a 5-G magnetic field, although some small sensitivity and linearity effects did exist. In 10-G fields, planar and reconstructed images were grossly distorted. Magnetic shielding placed across the collimator reduced the influence of the magnetic field but at a cost in sensitivity that varies with photon energy.     

磁性亲和分离的实验研究

目的：以磁性微球作为载体材料，使亲和分离过程更为简便迅速，并降低成本。方法与结果：使用自制的磁性微球偶联伴刀豆蛋白Ａ（ＣｏｎＡ）用于重组人血小板生成素（ｒｈＴＰＯ）的亲和富集；偶联抗体用于甲状腺素（Ｔ４）的放射免疫测定和水样中志贺菌的浓集和聚合酶链反应（ＰＣＲ）鉴定的前处理，效果也均较好，结论：本研究为上述３个领域的工作提供了一种有效可行而简便廉价的方法。     

Quantitative determination of magnetic force on a coronary stent in MRI

Purpose:

To introduce an analytical method for a quantitative determination of magnetic force on a coronary stent in the magnetic resonance imaging (MRI) magnet that is generally applicable to metallic implants. Magnetic forces on metallic implants in the MRI magnets are traditionally determined empirically by measuring deflection from the vertical plane at the central axis of the magnet and at the point of the largest force along the longitudinal axis of the magnet.

Materials and Methods:

Magnetic and chemical characterization of the stents was performed by a commercial magnetometer and energy‐dispersive X‐ray spectroscopy. Magnetic force on the stents fabricated of paramagnetic alloys (surgical stainless steel and cobalt–chromium) was determined by measuring the stent's magnetic dipole moment and employing the on‐axis magnetic field profile of an MRI magnet.

Results:

The maximum force on the stainless steel stent was found to be F_S,max = 0.18 mN, whereas on the cobalt–chromium stent it was F_C,max = 0.06 mN.

Conclusion:

The magnetic force on the investigated paramagnetic stents is even smaller than the gravitational force acting on the stents in the Earth's gravity field, so that it has no physiological impact on the stented vessels. J. Magn. Reson. Imaging 2013;37:391–397. © 2012 Wiley Periodicals, Inc.     

磁场、噪声、高温复合作用对大鼠热应激蛋白-70表达的影响

目的研究磁场、噪声、高温三因素复合作用对机体热应激蛋白-70(HSP70)表达的影响。方法采用三因素二水平正交方法[L8(27)]实验设计,用免疫组化ABC法测定大鼠肝脏、脾脏和脑组织的HSP70表达量。结果磁场对大鼠肝脏、脾脏和脑组织HSP70表达有影响(P<0.01或<0.05);高温对肝脏和脾脏组织中HSP70表达有影响(P<0.05)。结论磁场是影响HSP70表达的主因素,高温有一定的作用,磁场、高温、噪声三因素之间的交互作用不明显。     

模拟舰船磁场与噪声、高温复合对机体作用的方差分析

目的 研究模拟舰船两种剂量水平磁场复合噪声、高温对机体联合作用的特点。方法 采用有交互作用的三因素二水平的正交试验设计方法及方差分析法，按正交表L8（2^7）的要求安排8种复合暴露剂量组合，分别将兔和大鼠分为8个复合暴露组和8个对照组。结果 兔球结膜毛细血管管径、大鼠肝和脾脏HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．01），其次是高温（均为P〈0．05）,大鼠下丘脑AVP和大鼠脑组织HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．05）。兔血浆内皮素的分析结果显示出磁场与噪声交互作用所对应的F值有非常显著性意义（P〈0．01），磁场与噪声、高温三者之间交互作用所对应的F值也有显著性意义（P〈0．05）。结论 磁场是对上述指标影响的主因素，而高温也是重要因素；磁场与噪声有交互作用，磁场与噪声、高温三者之间也有交互作用；应该重视舰船环境因素对舰船人员的复合作用。     

Risks from magnetic fields and radiowaves in equipment for magnetic resonance tomography

The use of Nuclear Magnetic Resonance Imaging for diagnostic purposes requires a careful analysis of potential risks for workers, patients and public. Aim of this work is a review of the most important biological effects produced by static magnetic fields, radiofrequency fields and field gradients. It's common opinion in fact that the use of magnetic and radiofrequency fields instead of ionizing radiations fields is a safety warranty for patients and workers. Biological experiments in small animals and microorganisms show that also in this case some risks may be expected, due to the trend to employ as much high as possible magnetic fields (and therefore radiofrequency fields). The available data show that the normally used magnetic and radiofrequency fields are below the threshold for somatic effects but denote the necessity of a careful risks/benefit analysis for some patients groups (pacemakers and small surgical metallic implants carriers) and the need of extended and deep studies to specify a possible synergy of different physical agents and incidental oncogenic and teratogenic consequence on the patient.     

Short communication: assessment of environmental disturbances to the static magnetic field in magnetic resonance installations

The static magnetic field of MRI scanners can be affected by environmental factors. Magnetic resonance spectroscopy and functional imaging with single-shot echo-planar imaging (EPI) are particularly vulnerable to the movement of lifts, vehicles, trains and other large metallic masses in the vicinity. This work investigates the sensitivity of two different imaging techniques to assess disturbances of the static magnetic field: (i) phase changes in gradient-echo images of a uniform test object; and (ii) image displacement along the phase encoding direction in single-shot EPI images. For the latter a hexane sample was used, and the separation between CH2 and CH3 signals was taken as a reference. Both techniques were evaluated in a site known to be free of any significant environmental disturbances and validated by inducing a magnetic field disturbance. Both techniques provide valuable information in acceptance tests, allowing MRI users to evaluate and manage the environmental conditions surrounding a scanner. The single-shot EPI technique was found to be highly sensitive, being expected to detect magnetic field fluctuations down to 0.005 parts per million (ppm). The phase images method was found to be less sensitive (0.02 ppm) but is more easily available. The single-shot EPI technique was used in acceptance tests and environmental disturbances to the magnetic field of the order of 0.04 ppm were measured at the isocentre on two separate occasions.     

Acid and alkaline phosphatase activity in bone following intense magnetic field irradiation of short duration

Consideration of the biological effects of electromagnetic radiation is particularly important with regard to bone metabolism. Magnetic fields have been applied to the treatment of bone fractures, and similar fields are employed in the visualization of skeletal structures through magnetic resonance imaging (MRI). The present investigation addressed the effect of MRI-intensity (1 Tesla) magnetic fields on enzymatic indices of bone metabolism. Mice were exposed to intense static (direct current) magnetic fields for 30 min on each of 10 successive days. After this exposure regimen the primary spongiosum of the humerus was assayed for acid and alkaline phosphatase activity. No significant difference was detected in tissue levels of either enzyme in bones from control (n = 10), sham-exposed (n = 10), and magnetic field-exposed (n = 10) mice. These results suggested that the effects of magnetic field irradiation do not appear to involve modification of the activities of regulatory enzymes in bone.     

Biologic effects of the static magnetic field generated by a 0.5 T magnetic resonance tomograph on the enzyme activity of catalase and creatine kinase in the rat]

PURPOSE: We investigated possible alterations in the enzyme activity of catalase and isozyme MB-creatine kinase induced by prolonged exposure of laboratory rodents to a static magnetic field generated by a .5 T Magnetic Resonance unit. MATERIAL AND METHODS: Thirty Wistar albino mice were divided into two groups of 15 mice, one to be exposed to the static magnetic field for 12 hours and the other to be kept in the same environmental conditions as a control group. Immediately after the exposure a peripheral venous blood sample was collected, the cardiac muscle was removed from the mice and the enzyme activity of catalase and MB-creatine kinase were assayed using the spectrophotometric analysis. RESULTS: No statistically significant variation was detected between the enzyme activity of catalase and MB-creatine kinase in the serum and cardiac muscle of the exposed versus the control mice. In the mice exposed to the static magnetic field the enzyme activity of serum and cardiac muscle catalase were respectively .2154 U/L and .0707 U/L after 10 minutes; they were; .2699 U/L and .0946 U/L after 160 minutes. In the control mice the enzyme activity of serum and cardiac muscle catalase were respectively .1941 U/L and .0707 U/L after 10 minutes; they were .2061 U/L and .1068 U/L after 160 minutes. The enzyme activity of MB-creatine kinase in mice was measured in the exposed (80.8 U/L) versus the control (79.6 U/L) group: the difference does not exceed standard deviation. DISCUSSION AND CONCLUSION: Our results seem to exclude any alteration in the activity of catalase and MB-CK after 12 hours' exposure to the static magnetic field. However some homeostatic mechanisms peculiar to pluricellular organisms might act in vivo to adapt to the effects of the static magnetic field during exposure.     

Quantitative MR susceptibility mapping using piece‐wise constant regularized inversion of the magnetic field

Magnetic properties characterized by susceptibility and chemical shift linearly modify the local magnetic field experienced by spins. A piece‐wise constant solution using magnetic resonance imaging is found to the challenging inversion problem from field to magnetic properties. The magnetic field shifts were estimated from MR phase images. The MR magnitude images were segmented into many regions of uniform magnetic properties. Standard linear regression using the calculated magnetic field from each region allowed accurate susceptibility quantification. The technique was experimentally validated on a variety of samples including water, vegetable oil, air, Gadolinium, and superparamagnetic iron oxides. Susceptibility was measured with a precision better than 0.1 ppm, in a range of 10 ppm. In vivo feasibility was shown on the forearm for which soft‐tissue, cortical bone, and bone marrow susceptibility, and chemical shift values in good agreement with literature data were obtained. Magn Reson Med 60:1003–1009, 2008. © 2008 Wiley‐Liss, Inc.