^235U,^147Pm,^153Sm单独及混合照射时对骨肉瘤细胞的增殖抑制作用

本研究运用四氮唑（ＭＴＴ）显色反应,观察了＾２３５Ｕ,＾１４７Ｐｍ,＾１５３Ｓｍ单独及混合照射骨肉瘤细胞时,对瘤细胞增殖抑制作用的程度比较,结果表明,各核素单独照射（照射用放射性活度为：＾２３５Ｕ,１２８．４Ｂｑ;＾１４７Ｐｍ,７．４×１０＾５Ｂｑ;＾１５３Ｓｍ,７．４×１０＾５Ｂｑ）及混合照射（＾２３５Ｕ＋＾１４７Ｐｍ,＾２３５Ｕ＋＾１５３Ｓｍ,＾１４７Ｐｍ＋＾１５３Ｓｍ,其放射性活度均为各自单     

钐153—乙二胺四甲撑膦和氯化锶对多发性骨转移瘤患者免疫状态的影响

为探讨钐１５３－乙二胺四甲撑膦酸（＾１５３Ｓｍ－ＥＤＴＭＰ）和氯化锶（＾８９ＳｒＣｌ２）对多发性骨转移瘤患者免疫状态的影响,用＾１５３Ｓｍ－ＥＤＴＭＰ和＾８９ＳｒＣｌ２治疗多发性骨转移瘤病人８６例。分别测定患者外周血红细胞、白细胞、Ｔ淋巴细胞亚群和血清中免疫球蛋白的含量及肿瘤坏死因子水平。结果表明,单次＾１５３Ｓｍ－ＥＤＴＭＰ和＾８９ＳｍＣｌ２治疗多发性骨转移瘤患者外周血红细胞、Ｔ淋巴细胞亚群和血     

亲和素-生物素系统的153Sm标记及其生物学分布动力学的研究

选用＾１５３Ｓｍ对生物素进行放射性标记,然后利用亲和素和链霉亲和素与生物素的高亲合力特性,再对亲和素和链霉亲和素进行＾１５３Ｓｍ的标记,观察到大鼠和小鼠体内的血清除率和生物学分布,并与＾１５３ＳｍＣｌ３和＾１５３Ｓｍ－ＤＴＰＡ的生物学分布进行比较。结果表明,＾１５３Ｓｍ标记的亲和素血素除迅速,肝肾放射性摄取高;＾１５３Ｓｍ标记的链霉亲和素血清除缓慢,肝、脾、肾等脏器和血液中滞留量高;而＾１５３Ｓｍ     

^153Sm—骨膦（Cl2MDP）的制备和初步动物实验

研究了＾１５３Ｓｍ－Ｃｌ２ＭＤＰ的制备和体外稳定性，对其在动物体内分布和血液清除进行评价，并与＾１５３Ｓｍ－ＥＤＴＭＰ进行比较，实验结果表明＾１５３Ｓｍ－Ｃｌ２ＭＤＰ具有良好的体外稳定性，骨中摄取量高，血液清除较快；与＾１５３Ｓｍ－ＥＤＴＭＰ比较，血液清除慢，但肝脏摄取量比＾１５３Ｓｍ－ＥＤＴＭＰ高１０倍，故１５３Ｓｍ－Ｃｌ２ＭＤＰ不是一种理想的骨肿瘤治疗剂。     

^153Sm—树脂微球的制备和兔股骨血流量测定

制备了＾１５３Ｓｍ－树脂微球（ＲＭＳ），观察了ｐＨ和反应时间对树脂吸附的影响以及＾１５３Ｓｍ－ＲＭＳ的体外稳定性，同时用＾１５３Ｓｍ－ＲＭＳ测定兔股骨血流量，评价脂质清除剂对甾类激素处理的兔股骨血流量的改善。     

亲肿瘤显像剂^99Tc^m（V）—DMSA显像对^153Sm—EDTMP治疗骨转移癌的疗效评价

使用亲肿瘤显像剂＾９９Ｔｃ＾ｍ（Ｖ）－ＤＭＳＡ,对１６例经＾１５３Ｓｍ－ＥＤＴＭＰ治疗２～８个疗程后的骨转移癌患者进行随访显像研究。结果表明,中轴骨转移灶的消失率为４８．１％,四枝骨转移灶消失率为４１．９％,总有骨转移灶消失率为４５．８％,＾９９Ｔｃ＾ｍ（Ｖ）－ＤＭＳＡ具有亲肿瘤特性和亲骨性,对于＾１５３Ｓｍ－ＥＤＴＭＰ治疗骨转移癌疗效的随访,具有理论上的可信性和客观性;对于＾１５３Ｓｍ－ＥＤＴＭ     

EDTMP与Sm的摩尔比对^153Sm—EDTMP稳定性的影响

对不同条件下ＥＤＴＭＰ与Ｓｍ的摩尔比对高比活度或者低比活率＾１５３Ｓｍ－ＥＤＴＭＰ在肝脏中摄陬量的影响进行了研究。实验结果表明，ＥＤＴＭＰ怀富集靶的Ｓｍ摩尔比为１００：１或ＥＤＴＭＰ与天然靶的Ｓｍ摩尔比为６：１时，＾１５３Ｓｍ－ＥＤＴＭＰ在肝脏中摄取量可小于０．５％；同时发现辐射剂量和磷酸缓冲溶液对＾１５３Ｓｍ－ＥＤＴＭＰ的稳定性也也有影响。     

天然靶制^153Sm照射条件研究

在重水研究堆和轻水游泳池反应堆中，对不同靶型天然丰度的＾１５２Ｓｍ靶照射条件进行研究，实验结果表明，在游泳池反应堆宜于采用液体靶照射，＾１５３Ｓｍ的比活度比在重水研究中采用固体靶提高了２倍，天然钐靶照射后＾１５３Ｓｍ的核纯度大于９９％，满足临床治疗使用要求。     

天然靶制备^153Sm—EDTMP的质量控制

采用ＨＰＬＣ法对原材料ＥＤＴＭＰ，非放射性Ｓｍ－ＥＤＴＭＰ和＾１５３Ｓｍ－ＥＤＴＭＰ进行分析，结果表明：原材料没有其它有机杂质；天然钐靶堆照后的放射性核纯度为９９．７％，＾１５３Ｓｍ－ＥＤＴＭＰ的放射性浓度〈１．８５ＧＢｑ／ｍｌ时，自辐射分解不会影响使用。     

用于放射性滑膜切除的^153Sm—Citrate—HA的制备

介绍一种新放射性药物即钐［＾１５３Ｓｍ］－柠檬酸－羟基磷灰石，采用转换络合法进行标记。先将钐［＾１５３Ｓｍ］与柠檬酸络合，然后转换络合为羟基磷灰石（ＨＡ）的标记物，ＨＡ的络合容量约５ｍｇ（以Ｓｍ２Ｏ３计），标记物粒度主要为２－１０μｍ，标记率高达９８％。体外稳定性研究表明：标记物在生理盐水和人血浆蛋白溶液中放置三个半衰期，＾１５３Ｓｍ的总游离量小于２％。正常兔左后膝关节注射１４．８ＭＢｑ（４００μ     

153Sm-EDTMP诱发骨肉瘤细胞凋亡的荧光显微镜形态和增生抑制研究

通过荧光显微镜观察,发现骨肉瘤细胞受到     

DNA gel electrophoretic and microaut oradiographic studies on apoptosis in bone tumor cells after exposure with ^153Sm—EDTMP

The apoptosis in bone tumor cells is studied after ^153Sm-EDTMP irradiation.Fragmented DNA is analyzed by agarose gel electrophoresis.Experimental observations show that 153Sm-EDTMP exposure induces the internucleosomal DNA damage in bone tumor cells the DNA ladder pattern formation in bone tumor cells is show.At the same time,the microautoradiographic study indicates that ^153Sm-EDTMP could permeate through cell membrane and duisplays membrane-seeking condensation in bone tumor cells.Soon afterwards ^153Sm-EDTMP could be phagocytized by the tuymor cells and distributed in cytoplasm as well as nucleus in the form of phagosome.with the prolongation of observing time,the membrane-bounded apoptotic bodies are observed.     

Fluorescence microscopic morphology and inhibition rate studies on apoptosis of osteosarcoma cells induced by 153Sm

The apoptosis of osteosarcoma cells treated with irradiation by ^153Sm－EDTMPwas studied,The morphological changes in osteosarcoma cells were observed by fluorescence microscopy,It was found that osteosarcoma cells exposed with ^153Sm－EDTMP displayed significant nuclear fragmentation and marked pyknosis ,With the prolongation of observing period,the membrane bound apoptotic bodies formation was observed,It should be noted,that with the lenghening of irradiation time by ^153Sm－EDTMP,the inhibiton rate of proliferation of osteosarcoma cells increased progressively.     

Studies on apoptosis in bone tumor cells induced by 153Sm

The apoptosis in human bone tumor cells induced by internal irradiation with ^153Sm was studied. The morphological changes in bone tumor cells were observed by electronic and fluorescent microscopy, as well as DNA agarose gel eletrophoresis. DNA chain fragmentation, microautoradiographic tracing and the inhibition rate of proliferation in bone tumor cells exposed to ^153Srn with different duration time were examined. It was demonstrated that the bone tumor cells exposed to ^153Sm displayed nuclear fragmentation, pyknosis, margination of condensed chromatin, and formation of membrane bounded apoptotic bodies, whereas the percentage of DNA chain fragmentation of bone tumor cells increases in direct proportion to the duration of irradiation with ^153Sm, as well as DNA ladder formation in apoptotic cells. Also a marked inhibition effect of proliferation in bone tumor cells after exposure with ^153Sm was observed.     

DNA gel electrophoretic and microaut oradiographic studies on apoptosisin bone tumor cells after exposure with 153Sm-EDTMP

The apoptosis in bone tumor cells is studied after ¹⁵³Sm-EDTMP irradiation. Fragmented DNA is analyzed by agarose gel electrophoresis.Experimental observations show that ¹⁵³Sm-EDTMP exposureinduces the internucleosomal DNA damage in bone tumor cells the DNAladder pattern formation in bone tumor cells is shown. At the same time,the microautoradiographic study indicates that ¹⁵³153Sm-EDTMP could permeate through cell membrane and displays membrane-seeking condensation in bone tumor cells. Soon afterwards ¹⁵³Sm-EDTMP could be phagocytized by the tumor cells and distributed in cytoplasm as well as nucleus in the form of phagosome. With the prolongation of observing time, the membrane-bounded apoptotic bodies are observed.     

~（153）Sm－EDTMP治疗50例肿瘤性骨痛临床观察

５０例不同癌症患者用１５３Ｓｍ－ＥＤＴＭＰ治疗后７６％患者的骨痛有不程度的减轻，骨痛消失率达２０％，骨痛缓解时限１—２个月者为６０％。１０例患者９９ｍＴｃ－ＭＤＰ骨显像患／健侧值与１５３Ｓｍ－ＥＤＴＭＰ相隔１个月两个疗程骨显像患／健侧值自身对照（Ｐ＞０．０５）．表明１５３Ｓｍ－ＥＤＴＭＰ对缓解骨痛、控制临床症状，提高癌症患者的生活质量，作为一种姑息性治疗手段具有明显的临床推广和应用价值．     

钐153-乙二胺四甲撑膦和氯化锶对多发性骨转移瘤患者免疫状态的影响

为探讨钐１５３－乙二胺四甲撑膦酸（~（１５３）Ｓｍ－ＥＤＴＭＰ）和氯化锶（~（８９）ＳｒＣｌ_２）对多发性骨转移瘤 患者免疫状态的影响,用~（１５３）Ｓｍ－ＥＤＴＭＰ和~（８９）ＳｒＣｌ_２治疗多发性骨转移瘤病人８６例。分别测定患 者外周血红细胞、白细胞、Ｔ淋巴细胞亚群和血清中免疫球蛋白的含量及肿瘤坏死因子水平。 结果表明,单次~（１５３）Ｓｍ－ＥＤＴＭＰ和~（８９）ＳｒＣｌ_２治疗多发性骨转移瘤患者外周血红细胞、 Ｔ淋巴细胞 亚群和血清中免疫球蛋白的含量及肿瘤坏死因子水平治疗前后和两治疗组之间比较无显著差异 （Ｐ＜０．０５）,白细胞虽有下降,但仍在正常范围内;随着药物放射剂量增加,病人骨髓毒性增 大,外周血红细胞、白细胞和血清中免疫球蛋白的含量降低,而Ｔ淋巴细胞亚群的分布未见变 化,说明常规用量的~（１５３）Ｓｍ－ＥＤＴＭＰ和~（８９）ＳｒＣｌ_２对患者的Ｔ淋巴细胞亚群、免疫球蛋白及肿瘤坏 死因子水平等无明显影响,但随着放射性剂量的增加,病人的免疫功能受到影响难以避免,并 可能以体液免疫首先受到抑制。     

153Sm-EDTMP与云克联合治疗转移性骨肿瘤疼痛的临床价值

为探讨^153Sm-EDTMP（^153钐－乙二胺四亚甲基膦酸）与云克（^99Tc-MDP，即^99锝－亚甲基二膦酸盐）联合治疗转移性骨肿瘤疼痛的临床价值。对210例癌骨转移患者分别为^153Sm-EDTMP单独治疗或与云克联合治疗，观察其疗效。结果显示，^153Sm-EDTMP单独治疗组，止痛有效率为83．7％，转移灶消失或缩小的总有效率为21．6％；^153Sm-EDTMP与云克静脉滴注联合治疗组，止痛有效率为94．7％，转移灶消失或缩小的总有效率为35．1％。后者明显高于单独治疗组。表明^153Sm-EDTMP联合云克静脉滴注对恶性肿瘤多发性骨转移所致疼痛有明显疗效，且安全无副作用。联合治疗组疗效优于单独治疗组。     

Measurement of 153Sm-EDTMP bone uptake by whole-body scintigraphy and its application to individualized treatment dosimetry of bone metastasis

1 INTRODUCTIONSamarium-153 ethylenedialninetetramethylene phosphonic acid ("'Sin-EDTMP) iselective in the palation of painful bony metastases[1]. Pain relief is seen in 60%~90%of patients treated with "'Sin-EDTMP, and the onset Of pain relief generally beginswithin 1 week of administration. The critical organ in 153Sin-EDTMP therapy is thered bone marrow and myelotoalcity can be a significant side effect of the administrationof therapeutic activities of 153Sin-EDTMP[2]. There is…     

Electron microscopic observations and DNA chain fragmentation studies on apoptosis in bone tumor cells induced by ~(153)Sm-EDTMP

ＥｌｅｃｔｒｏｎｍｉｃｒｏｓｃｏｐｉｃｏｂｓｅｒｖａｔｉｏｎｓａｎｄＤＮＡｃｈａｉｎｆｒａｇｍｅｎｔａｔｉｏｎｓｔｕｄｉｅｓｏｎａｐｏｐｔｏｓｉｓｉｎｂｏｎｅｔｕｍｏｒｃｅｌｓｉｎｄｕｃｅｄｂｙ１５３ＳｍＥＤＴＭＰＺｈｕＳｈｏｕＰｅｎｇ，Ｘｉａ...