^89SrCl2与^153Sm-乙二胺四亚甲基膦酸治疗骨转移癌的对比研究

目的对比研究^89SrCl2和^153Sm-乙二胺四亚甲基膦酸（^153Sm-EDTMP）治疗骨转移癌疗效。方法120例骨转移患者随机分为SOSrCl2治疗组和^153Sm-EDTMP治疗组,分别为69例和51例,^89SrCl2剂量为1．11-2．22MBq／kg,^153Sm-EDTMP剂量为25．9～37．0MBq／kg,3-6月复查SPECT,对止痛效果、转移灶变化及不良反应进行比较分析。结果^89SrCl2组总有效率、显效、有效、无效分别为92．8％、69．6％、23．3％、7．2％;^153Sm-EDTMP组的总有效率、显效、有效、无效分别为94．2％、66．7％、27．5％、5．8％,两组比较的差异无统计学意义（χ^2=4．98,P〉0．05）;^89SrCl2治疗组骨转移病灶Ⅰ级（变淡,缩小或消失,无新增病灶出现）为56．5％,^153Sm-EDTMP组为54．9％,两组比较的差异无统计学意义（χ^2=4．81,P〉0．05）;骨髓抑制情况（白细胞和血小板中任一项降低）分别为40．8％和59．2％,两组比较的差异有统计学意义（r=7．45,P〈0．05）。结论^153sm-EDTMP和^89SrCl2控制乳腺癌、前列腺癌及大多数肺癌骨转移疼痛有效,可根据经济条件选择相应药物。^89SrCl2疗效持久,相对骨髓抑制较小,更安全可靠,可作为早期骨转移患者的首选药物。     

骨转移瘤患者 89SrCl2治疗后免疫功能的变化

目的　研究骨转移瘤患者89SrCl2 治疗后免疫功能变化。方法　选择已确诊骨转移瘤经89SrCl2 治疗的患者 4 2例 ,与正常对照组 2 0例比较患者治疗前后T淋巴细胞亚群CD 4、CD 8、CD 4 CD 8值 ,分析治疗有效组和无效组免疫指标及病灶数变化。结果　骨转移瘤患者治疗前各组间免疫学指标差异无显著性 (P >0 0 5 ) ,对照组与骨转移瘤患者及骨转移瘤患者治疗前后各免疫学指标差异均有显著性 (P <0 0 5 )。治疗后有效组和无效组间各指标差异亦有显著性 (P <0 0 5 )。经89SrCl2治疗 ,4 2例患者中 37例 (88 10 % )免疫功能得到改善 ,以疼痛评分为指标则 4 2例患者中 33例(78 5 7% )有效 ,2 9例 (6 9 0 5 % )病灶数减少。结论　89SrCl2 治疗骨转移瘤有效 ,并可提高免疫功能 ;治疗后免疫指标变化可反映治疗效果。     

153Sm-EDTMP吸收剂量的MonteCarlo和MIRD算法比较

目的以153Sm-乙二胺四甲撑膦酸(153Sm-EDTMP)治疗鼻咽癌多发性骨转移为例,分别用蒙特卡罗法(Monte Carlo,MC)和MIRD方法计算153Sm-EDTMP治疗后病灶和骨髓等靶器官的吸收剂量,探讨其临床应用之不同.方法基于病人时序性SPECT/CT扫描和累积尿液的放射性测定,利用优化的MC EGS4程序和MIRD方法分别计算病灶和其他靶器官的吸收剂量.结果MC EGS4法计算结果提示病灶内剂量分布不均匀.患者注射153Sm-EDTMP 33.6×37 MBq,左髂骨转移病灶最高吸收剂量约为5.6 Gy,病灶边缘的吸收剂量为2.0 Gy,以病灶区最高剂量点为参考点,则椎体、皮质、骨髓、脊髓和盆腔组织仅相当于最高剂量的37%、12%、13%、21%和2%;MIRD方法的计算数据仅能粗略提示全身红骨髓吸收剂量,为2.39 Gy.结论MC EGS4方法能准确计算病灶、骨髓和其他靶器官的内照射吸收剂量,故可以真正指导核素临床治疗;而MIRD仅能大致评估153Sm-EDTMP的骨髓毒性.     

89SrCL2与唑来膦酸联合治疗乳腺癌转移性骨肿瘤的疗效分析

目的：探讨放射性核素二氯化锶（89SrCl2）联合唑来膦酸治疗激素依赖型乳腺癌转移性骨肿瘤的临床疗效。方法回顾性分析64例激素依赖型乳腺癌转移性骨肿瘤患者的临床资料,将所有患者分为3组：89SrCl2治疗组22例;唑来膦酸治疗组21例;89SrCl2联合唑来膦酸治疗组21例;观察治疗后转移病灶疗效、骨痛缓解情况、生活质量状况、骨髓抑制反应情况。结果89SrCl2治疗骨转移病灶有效率为36.4%（8/22）,视觉模拟评分下降率为77.3%（17/22）,全身状况KPS评分提高率为63.6%（14/22）,27.2%（6/22）的患者出现骨髓抑制反应;唑来膦酸治疗后骨转移病灶有效率为33.3%（7/21）,视觉模拟评分下降率为71.4%（15/21）,全身状况KPS评分提高率为52.4%（11/21）,19.0%（4/21）的患者出现骨髓抑制反应;89SrCl2联合唑来膦酸治疗骨转移病灶有效率为42.9%（9/21）,视觉评分下降率为90.5%（19/21）,全身状况KPS评分提高率为90.5%（19/21）,33.3%（7/21）的患者出现骨髓抑制反应。结论89SrCl2联合唑来膦酸对激素依赖型乳腺癌转移性骨肿瘤的疗效明显,不良反应小,联合治疗效果优于89SrCl2和唑来膦酸单独治疗。     

89SrCl联合依班膦酸钠治疗多发性骨转移癌疼痛

目的 观察89SrCl2联合依班膦酸钠治疗多发性骨转移癌疼痛与单独应用依班膦酸钠或89SrCl2治疗的临床疗效。方法84例骨转移癌疼痛患者,分为3个治疗组,其中30例采用89SrCl,联合依班膦酸钠方法,26例采用单纯89SrCl2治疗,28例采用依班膦酸钠治疗。用SPSS13．0统计软件,疗效比较采用行×列表资料的r检验。结果联合治疗组骨痛缓解总有效率为96．6％（29／30）,依班膦酸钠组及89SrCl2治疗组总有效率分别为71．4％（20／28）和73．1％（19／26）。联合用药组与单独用药组治疗后骨痛缓解有效率（X2=7．497）,全身状况Kamofsky评分提高率[80．0％（24／30）与50．0％（14／28）,53．8％（14／26）,X2=35．476]和病灶治疗有效率[47．6％（50／105）与11．2％（11／98）,22．2％（20／90）,X2=6．564]间比较差异有统计学意义（P均〈0．05）。结论89SrCl2联合依班膦酸钠是治疗骨转移性癌疼痛较为有效和可行的方法。联合用药临床疗效优于单独用药。     

153Sm-EDTMP治疗转移癌性骨痛

目的 探讨影响^153Sm-乙二胺四亚甲基磷酸盐（EDTMP）治疗转移癌性骨痛疗效的相关因素。方法 按国际原子能机构区域合作计划组织中国多中心研究,3年内收集^153Sm-EDTMP治疗转移癌性骨痛234例,根据治疗响应分为有效及无效2组,比较其个人情况,临床特点,原发病种,骨转移特点及治疗方法等因素,以SAS软件进行分组与多因素分析。结果 183例治疗有效,51例治疗无效,2组间在年龄、非核素治疗、^153Sm-EDTMP用量、转移灶数目、占骨骼比重、放射性摄取程度等方面无明显差别。但无效组中男性（43例,84.3%）、肺癌（34例,66.7%）、脊柱、骨盆与下肢转移的比例明显不同于有效组。多因素分析证实患者性别、肿瘤类型和转移部位与治疗效果相关。结论 ^153Sm-EDTMP治疗对肺癌、男性和下半身转移者效果可能较差。     

唑来膦酸联合89Sr治疗前列腺癌骨转移的临床疗效

目的评估唑来膦酸联合89Sr治疗前列腺癌骨转移的临床疗效。方法74例前列腺癌骨转移患者按简单随机分组方法分为3组:唑来膦酸联合89Sr治疗组（A组）25例,年龄46~87岁,中位年龄66岁;单独给予唑来膦酸治疗组（B组）25例,年龄43~89岁,中位年龄65岁;单独给予89Sr治疗组（C组）24例,年龄47~85岁,中位年龄66岁。其中,B组和C组为对照组。随访6个月,观察患者骨骼疼痛缓解情况和骨转移病灶数目改善情况。结果3组患者的基线特征相似。治疗后,A组总的疼痛缓解率为88.0%,B组和C组分别为72.0%和79.2%,A组疼痛缓解情况与B组和C组相比差异有统计学意义（χ2=8.959,P < 0.05）。A组骨转移病灶好转率为88.0%,B组和C组分别为44.0%和75.0%,A组病灶好转情况分别与B组、C组相比,差异有统计学意义（χ2=9.096,P < 0.05）。结论唑来膦酸联合89Sr治疗前列腺癌骨转移较单独给药具有更好的缓解疼痛作用,89Sr治疗可有效减少骨转移病灶,提高患者的生活质量。     

烟酰胺和碳合氧增敏89Sr治疗多发性骨转移癌的临床研究

目的评价烟酰胺和碳合氧（Carbogen）增敏^89Sr治疗多发性骨转移癌的作用、骨痛的缓解及毒副反应。方法97例恶性肿瘤多发性骨转移患者随机分为4组：烟酰胺＋Carbogen＋^89Sr治疗组（A组）；烟酰胺＋^89Sr治疗组（B组）；Carbogen＋^89Sr治疗组（C组）；^89Sr治疗组（D组）。^89SrCl2治疗采用1．48-2．22MBq／kg，静脉注射。注射^89Sr前1h开始给予烟酰胺，6g／d，分3次口服，连服5d。首次口服烟酰胺后开始吸入Carbogen（95％O2＋5％CO2）气体，6L／min，10min，每日1次，连续5d。结果A组治疗后骨痛的缓解及生活质量较B组、C组及D组有效率高（91．7％、77．3％、76．0％和69．2％），且A组与D组比较差异有统计学意义（P=0．048）。治疗后3个月复发性骨转移癌全身骨显像反应，各组之间差异无统计学意义。各组病人治疗后均有Ⅰ-Ⅱ度骨髓抑制，各组之间差异无统计学意义。结论烟酰胺＋Carbogen＋^89Sr治疗多发性骨转移癌，对骨痛的缓解及生活质量的改善有更好的疗效，且未增加^89Sr的治疗毒性反应。     

~(89)Sr治疗乳腺癌转移性骨痛的疗效评价

目的　评价89SrCl2 对乳腺癌转移性骨痛的临床疗效。方法　对 86例乳腺癌骨转移患者按体重静脉注射89Sr 1.48～ 2 .2 2MBq/kg。结果　治疗后骨痛减轻或消失 72例 ,总有效率为83 72 % ;治疗后骨显像有 5 9.30 % (5 1例 )骨转移灶代谢减低 ,治疗前后ROI比值比较 ,P <0 .0 5。治疗后有 2 7.90 % (2 4例 )出现Ⅰ～Ⅱ度血液学毒性反应 ,对心、肝、肾功能几乎没有影响。结论　89Sr对缓解乳腺癌骨转移瘤疼痛有较好疗效 ,并有一定的治疗作用 ,副作用小 ,可重复用药。     

89Sr治疗乳腺癌和前列腺癌多发性骨转移的临床观察

目的 探讨放射性核素89Sr治疗乳腺癌和前列腺癌多发性骨转移患者的临床效果.方法 回顾性分析30例乳腺癌和40例前列腺癌多发性骨转移患者接受89Sr治疗的病例资料,采用Karnofsky评分量表和骨显像方法进行疗效评估.结果 乳腺癌组的止痛总有效率为79%,前列腺癌组的止痛总有效率为85%,两组患者之间差异无统计学意义(x2=0.78,P＞0.05).两组患者的生存质量均有明显改善,治疗前后两组患者的Karnofsky评分均有明显提高(t=2.46,P＜0.05;t=2.68,P＜0.05).治疗后两组患者均未见明显骨髓抑制与肝肾功能损伤.结论 89Sr治疗乳腺癌和前列腺癌多发性骨转移止痛效果良好,患者生存质量有明显提高.     

ESR dosimetry of 89Sr and 153Sm in bone.

The radiation absorbed dose in the rabbit bone delivered by 153Sm-EDTMP (samarium ethylenediaminetetra methylene diphosphonic acid) and 89SRCl2 (strontium chloride) was measured by means of electron spin resonance (ESR). These radioisotopes are used in systemic radiotherapy for palliation of painful bone metastases. The knowledge of the dose is important in order to avoid side effects to the bone marrow. The ESR radiation dose signal was calibrated by the additive dose method using cobalt-60 gamma rays. For 153Sm-EDTMP, the bone doses in three rabbits were (4 +/- 2), (5 +/- 1) and (5 +/- 2) cGy kg/MBq. For 89SrCl2, a dose of (2 +/- 1) cGy kg/MBq was found in one rabbit.     

Prospective 153Sm-EDTMP therapy dosimetry by whole-body scintigraphy.

Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) effectively palliates painful bony metastases, but the standard recommended administered activity of 38 MBq.kg-1 may lead to significant myelotoxicity. Prospective individual dosimetry by urine collection and counting allow the bone marrow radiation dose to be limited to 2 Gy. Our novel whole-body scintigraphic method for prospective dosimetry was compared with the 5 h urine collection technique in 10 patients with bone metastases. Anterior and posterior whole-body images were obtained using identical acquisition parameters 10 min and 5 h after the intravenous injection of 740 MBq 153Sm-EDTMP. Total counts in each imaging study were corrected for background activity and time of injection and the bone activity at 5 h was determined. Bone activity was also calculated from a complete urine collection over 5 h, and these two values were compared. MIRD formulae were applied to calculate the radiation absorbed dose to the bone marrow from the injected activity. The total activity delivering a dose of 2 Gy to the bone marrow was then determined and constituted the amount given for therapy. Values for bone activity determined by imaging and by urine counting were concordant in all patients (correlation coefficient = 0.98). The total administered activity of 153Sm-EDTMP predicted on a 2 Gy bone marrow dose varied between 35 and 63% of the standard recommended regimen of 37 MBq.kg-1 and pain relief was experienced by eight of the ten patients. Administration of 153Sm-EDTMP according to the supplier's recommendations would have delivered bone marrow doses of 3.27-5.90 Gy in our patients, doses at which myelotoxicity would have been anticipated.     

153Sm-EDTMP and melphalan chemoradiotherapy regimen for bone marrow ablation prior to marrow transplantation: an experimental model in the rat.

Chemoradiotherapy with melphalan and 153Sm-ethylenediaminetetramethylene phosphonate (EDTMP) was used to ablate bone marrow in WAG rats which were subsequently rescued by marrow transplantation. Internal irradiation of bone marrow with high doses of up to 3.5 GBq kg-1 153Sm-EDTMP alone produced profound, but self-limiting, myelosuppression and all animals recovered spontaneously. Melphalan alone in doses of 9.5 mg kg-1 also caused transient myelosuppression without mortality. However, the combination of 9.5 mg kg-1 melphalan and 555 MBq kg-1 153Sm-EDTMP caused marrow ablation and death in 80% of animals. The mortality of this chemoradiotherapy regimen was reduced to 7% by sequential administration of 153Sm-EDTMP on day 0 and melphalan on day 5 followed by marrow transfusion of 7.5 x 10(7) cells on day 6. These results were comparable to those obtained following bone marrow transplantation 24 h after lethal total body external beam irradiation. In the inbred WAG rat experimental model the sequential chemoradiotherapeutic regimen of internal irradiation with 153Sm-EDTMP followed by chemotherapy with melphalan was demonstrated to ablate bone marrow effectively whilst preserving the capacity for recovery following marrow transplantation.     

99Tc-亚甲基二膦酸盐与153Sm-乙二胺四亚甲基膦酸对骨侵袭和骨质溶解抑制作用的对比研究

目的 对比观察99c-亚甲基二膦酸盐(99Tc-MDP)与153Sm-乙二胺四亚甲基膦酸(153Sm-EDTMP)对Walker256癌细胞引起的大鼠骨侵袭和骨质溶解的抑制作用及二者对移植瘤细胞的影响.方法 建立Walker 256癌大鼠骨侵袭和骨质溶解模型.设空白对照组、99Tc-MDP治疗组、153Sm-EDTMP治疗组、99Tc-MDP+153Sm-EDTMP治疗组,采用99Tcm-MDP全身骨显像、骨骼X线片及胫骨病理切片方法观察两种药物单独或联合应用对荷瘤大鼠骨侵袭和骨质溶解的抑制作用,并通过流式细胞仪分析两种药物对移植瘤细胞的影响.结果 与对照组相比,99Tc-MDP治疗组、153Sm-EDTMP治疗组、99Tc-MDP+153Sm-EDTMP治疗组均能明显抑制荷瘤大鼠骨侵袭和骨质溶解(确切概率法:P<0.05).两种药物联合应用与单独应用相比未见明显差异.各治疗组移植瘤细胞的凋亡率明显高于对照组,S期的细胞比例明显下降,二者联合应用的作用更明显.结论 ①99Tc-MDP及153Sm-EDTMP对荷Walker 256癌大鼠均有抑制骨侵袭和骨质溶解的作用;②两种药物在诱导移植瘤细胞凋亡、抑制移植瘤细胞增殖方面均有一定作用,二者联合应用的作用更明显.     

SPECT显像评价骨肿瘤治疗剂^153Sm—EDTMP在骨转移灶的保留率

本文报道了用１５３Ｓｍ－ＥＤＴＭＰ治疗骨转移癌３２例，用ＳＰＥＣＴ显像法动态连续观察转移灶和正常骨胳各时相的保留率，发现骨转移灶和正常骨对１５３Ｓｍ－ＥＤＴＭＰ的清除在４８小时以前有显著性差异，而在４８小时以后无显著性差异。资料又证明骨转移癌病人的尿液和１５３Ｓｍ－ＥＤＴＭＰ原液纸层析测定其Ｒｆ值是完全相同的。表明１５３Ｓｍ－ＥＤＴＭＰ以骨中清除是以原形物的方式入血，入血的１５３Ｓｍ－ＥＤＴＭＰ又被代谢活跃的转移灶再摄取，结果致转移灶的放射性活度增加，而正常骨代谢低于转移灶，再摄取的量极少，因而两者在４８小时以前有差异，而４８小时以后清除到血中的量减少，再摄取减少，故无差别     

Effects of 153Sm-ethylenediaminetetramethylene phosphonate on physeal and articular cartilage in juvenile rabbits.

Previous studies reported that the radiopharmaceutical (153)Sm-ethylenediaminetetramethylene phosphonate ((153)Sm-EDTMP) is an effective component of multimodality therapy for the treatment of primary bone tumors. Therefore, (153)Sm-EDTMP may prove to be an integral component of therapy for the treatment of juvenile osteosarcoma. The purpose of this study was to determine the effects of intravenous administration of (153)Sm-EDTMP on the developing physeal and articular cartilage of healthy, juvenile rabbits. METHODS: Sixteen healthy 8-wk-old male New Zealand White rabbits were assigned to 1 of 2 groups: treatment (n = 12) and control (n = 4). (153)Sm-EDTMP was administered to the treatment group at 37 MBq/kg (1 mCi/kg). The animals were sacrificed at 16 wk of age, and the physeal cartilage of multiple bones was evaluated by use of histologic, immunohistochemical, and histomorphometric analyses. The overall changes in the lengths of the radius and the tibia between control and treatment groups were calculated and compared. Measurement data were combined for each group, and means +/- SEMs were determined. RESULTS: Significant differences in radial bone growth were present between the groups. Histologically, the physes of the treatment group were disrupted and chaotic in appearance. Significant differences in the immunoreactivity of type X collagen and matrix metalloproteinase-13 were seen between the groups, as these markers were positively expressed in the zone of hypertrophy of the control rabbits. CONCLUSION: Clinically significant damage to the developing physeal cartilage may occur as a result of the intravenous administration of (153)Sm-EDTMP at the dose studied.     

A practical guide to targeted therapy for bone pain palliation

Targeted radionuclide therapy is an effective and cost efficient treatment for multi-site metastatic bone pain. This paper discusses the physical characteristics of the licensed radiopharmaceuticals (153)Sm ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) ((153)Sm-EDTMP), (186)Re 1,1-hydroxyethylidenediphosphonate ((186)Re-HEDP) and (89)SrCl(2) and considers the factors influencing treatment choice in specific clinical settings. The advantages and practical limitations of this approach are discussed, with emphasis on defining criteria for patient selection and response monitoring. Opportunities for future research and development are outlined.     

A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases

AIM: The surface bone-seeking radiopharmaceuticals 188Re-HEDP, 186Re-HEDP and 153Sm-EDTMP, and the volume seeker 89Sr were investigated to determine the efficacy and toxicity in pain palliation of bone metastases. METHOD: The effect of treatment with 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr on pain symptoms, quality of life, and bone marrow function were studied. In total, 79 patients (18 with breast cancer and 61 with prostate cancer) were treated (31 patients with 188Re-HEDP, 15 patients each with 186Re-HEDP and 153Sm-EDTMP, and 18 patients with 89Sr). All patients were interviewed using standardized sets of questions before and after therapy weekly for 12 weeks. Blood counts were taken weekly for 6 weeks and after 12 weeks. RESULTS: In total, 73% of patients reported pain relief (77% after 188Re-HEDP, 67% after 186Re-HEDP 73% after 153Sm-EDTMP, and 72% after 89Sr). Fifteen percent of patients could discontinue their analgesics and were pain-free. Pain showed a decrease from 3.6+/-1.7 to a maximum of 2.2+/-1.8 at visual analogue scale in 10 steps (P<0.01). Patients described an improvement on the Karnofsky performance scale from 70+/-10% to 78+/-14% 12 weeks after treatment (P=0.15). There were eight patients with a thrombocytopenia grade I, two patients with grade II and one with grade III. The maximum nadir of platelet and leukocyte counts were observed between the 2nd to 5th week after treatment and was reversible within 12 weeks. There were no significant differences in pain palliation, Karnofsky performance status (KPS) and bone marrow toxicity between the different radionuclides (P=0.087-0.449). CONCLUSION: All radiopharmaceuticals were effective in pain palliation, without induction of severe side effects or significant differences in therapeutic efficacy or toxicity.