~(153)Sm-乙二胺四亚甲基膦酸对 Walker 256癌荷瘤大鼠骨侵袭骨溶解的抑制作用

目的研究１５３Ｓｍ－乙二胺四亚甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）对荷瘤大鼠骨侵袭、骨溶解的抑制作用。方法运用Ｘ线骨骼照片和胫骨病理切片，观察Ｗａｌｋｅｒ２５６癌大鼠模型的肿瘤骨侵袭和骨溶解情况。结果荷瘤大鼠静脉注射１５３Ｓｍ－ＥＤＴＭＰ７４，１４８ＭＢｇ／ｋｇ后，遭受Ｗａｌｋｅｒ２５６癌侵袭及发生骨溶解的胫骨数减少近一半，３７ＭＢｇ／ｋｇ组对癌的骨侵袭和骨溶解仍有抑制作用。但各组大鼠的移植瘤重量没有差异。结论１５３Ｓｍ－ＥＤＴＭＰ能抑制Ｗａｌｋｅｒ癌模型大鼠骨侵袭和骨溶解，但对移植瘤生长无抑制作用，故其抗癌骨侵袭、骨溶解的作用不是通过抑制动物移植瘤生长来实现的。     

^153Sm—EDTMP对癌症骨痛治疗和提高生活质量的价值

应用＾１５３Ｓｍ－ＥＤＴＭＰ，治疗各种骨继发性肿瘤４０例。静脉一次给予量为２９．６ＭＢｑ／ｋｇ（０．８ｍＣｉ／ｋｇ），其中７例接受重复治疗。随访时间为３０天～１０个月。给药前２周内＾９９ｍＴｃ－ＭＤＰ与给药后＾１５３Ｓｍ－ＥＤＴＭＰ全身骨显象观察比较。该药副作用轻微，止痛效果显著。本组显效９例，有效２４例，总有效率为８２．５％，骨痛得到控制，生活质量明显提高。     

^153Sm—EDTMP治疗肿瘤骨转移止痛效果相关因素分析

目的 分析影响＾１５３Ｓｍ－ＥＤＴＭＰ对肿瘤转移性骨痛治疗效果的相关因素，方法 对我院近两年使用＾１５３Ｓｍ－ＥＤＴＭＰ行内照射治疗的５９例肿瘤转移性骨病人进行回顾性分析，按年龄，病灶数量，不同肿瘤分组，单次剂量给予＾１５３Ｓｍ－ＥＤＴＭＰ１８．５－３７ＭＢｑ／ｋｇ静脉注射，第２天行全身骨显像现查放射分布情况，建立随访。结果 总有效率为９３．６％，在年龄组中，以老年组效果最好，止痛有效率为９６．９     

帕米膦酸二钠和^153Sm—EDTMP治疗骨继发性恶性肿瘤疗效对比 …

帕米膦酸二钠（ＡＰＤ）与＾１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物，为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和＾１５３Ｓｍ－ＥＤＴＭＰ组每组各２１例，结果显示：ＡＰＤ和＾１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ〉０．０５），ＡＰＤ与＾１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％，２３．８     

^153Sm—EDTMP治疗多发性骨转移癌

用１５３Ｓｍ－ＥＤＴＭＰ（ｅｔｈｙｌｅｎｅｄｉａｍｉｎｅｔｅｔｒａｍｅｔｈｙｌｅｎｅＰｈｏｓｐｈｏｎｉｃａｃｉｄ）治疗多发性骨转移癌６０例，其原发灶均经病理及细胞学证实。静脉一次给予量为１４．８～２９．６ＭＢｑ／ｋｇ体重，多数病人（５０／６０）按１８．５ＭＢｑ／ｋｇ体重计算治疗剂量，一般病人治疗１～４次，两次治疗间隔为４～８周。止痛有效率为８１．７％（４９／６０），给药前２周内９９ｍＴｃ－ＭＤＰ与给药后１５３Ｓｍ－ＥＤＴＭＰ全身骨显像进行观察比较。随访１～１２个月，认为１５３Ｓｍ－ＥＤＴＭＰ治疗多发性骨转移癌疗效好、副反应小，使用安全     

骨膦和（153）~Sm－EDTMP治疗骨转移癌

本文报道应用骨膦和／或１５３Ｓｍ－ＥＤＴＭＰ内照射治疗骨转移癌７４例。骨膦组２１例，１５３Ｓｍ－ＥＤＴＭＰ组２６例，对骨痛止痛有效率分别为８５．７％和８０．８％，对骨病变有效率分别为９．５％和１９．２％。而联合应用骨膦和１５３Ｓｍ－ＥＤＴＭＰ治疗３１例，止痛有效率和骨病变有效率分别为９３．５％和４５．２％，后者与前２组相比有显著差异（Ｐ＜０．０５）。三组毒副反应均少见。由此提示，骨膦＋１５３Ｓｍ－ＥＤＴＭＰ疗效显著，安全可靠，可能是当今治疗多发性骨转移癌的优选疗法。     

^153Sm—乙二胺四亚甲基磷酸盐治疗骨肿瘤转移性疼痛

本文介绍了一种新的肿瘤转移性疼痛治疗方法－＾１５３Ｓｍ－乙二胺四亚甲基磷酸盐（＾１５３Ｓｍ－ＥＤＴＭＰ）放射药物治疗法。＾１５３Ｓｍ－ＥＤＴＭＰ血液清除快，病变区骨摄取高，对正常组织及造血系统的毒副作用小。经临床近千例验证，＾１５３Ｓｍ－ＥＤＴＭＰ对肿瘤转移性骨痛的缓解率为７６％～９６％，治疗后转移灶完全消失占１０％。＾１５３Ｓｍ－ＥＤＴＭＰ治疗是临床常规治疗无效后缓解及治疗转移性骨痛的首选方法。     

乳腺癌多发性骨转移的预后和153Sm-EDTMP治疗结果

目的：分析乳腺癌多发性骨转移的预后和＾１５３Ｓｍ－乙二胺四甲基膦酸（ＥＤＴＭＰ）治疗效果。方法：回顾分析１９９２年至１９９８年１３１例接受了＾１５３Ｓｍ－ＥＤＴＭＰ治疗的乳腺癌多发性骨转移病人。所有病人经病理或细胞学证实为乳膛癌。骨转移灶经骨显像、Ｘ光片、ＣＴ和／或ＭＲＩ诊断证实。结果：全组病人总的５年生存率为５９％,骨转移后５年生存率和中位生存期分别为１８．５％和１５个月。转移局限于骨的病人比骨     

~（153）Sm─EDTMP对癌症骨痛治疗和提高生活质量的价值

应用１５３Ｓｍ─ＥＤＴＭＰ（ｅｔｈｙｌｅｎｅｄｉａｍｉｎｅｔｅｔｒａｍｅｔｈｙｌｅｎｔｐｈｏｓｐｈｏｎｉｃａｃｉｄ），治疗各种骨继发性肿瘤　　４０例。静脉一次给予量为２９．６ＭＢｑ／ｋｇ（０．８ｍＣｉ／ｋｇ），其中７例接受重复治疗。随访时间为３０天～１０个月。给药前２周内９９ｍＴｃ─ＭＤＰ与给药后１５３Ｓｍ─ＥＤＴＭＰ全身骨显象观察比较。该药副作用轻微，止痛效果显著。本组显效９例，有效２４例，总有效率为８２．５％，骨痛得到控制，生活质量明显提高。     

帕米膦酸二钠和~(153)Sm-EDTMP治疗骨继发性恶性肿瘤疗效对比研究

帕米膦酸二钠（ＡＰＤ）与１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物。为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和１５３Ｓｍ－ＥＤＴＭＰ组，每组各２１例，结果显示，ＡＰＤ和１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ＞０．０５）。ＡＰＤ与１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％、２３．８１％（Ｐ＜０．０５）。说明ＡＰＤ对转移病灶控制的效果更佳。两种药物毒副作用不大，患者均可耐受。     

An experimental rat model of local bone cancer invasion and its responsiveness to ethane-1-hydroxy-1,1-bis(phosphonate)

Line A Walker carcinoma differs from line B in that it does not elicit hypercalcemia and hypercalciuria when implanted in rats at various sites (s.c, i.m., intraaortically). However, Walker 256/A, unlike line B, may invade the tibia when implanted i.m. in the adjacent gastrocnemius muscle. This invasion was evaluated by measuring the increased weight of the bone and decreased calcium concentration per unit weight of the tibia, by reduced opacity to X-ray, and by the presence of tumor cells in the compact bone cortex. Ethane-1-hydroxy-1,1-bis(phosphonate), a diphosphonate derivative, at a dose of 10 to 30 mg/kg/day s.c., prevented cancer cell invasion of the tibia as judged by the above criteria. This inhibition was obtained with no apparent effect on the growth of Walker 256/A carcinoma.     

153Sm-EDTMP治疗多发骨转移瘤的剂量效应关系初步观察

Objective: To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo (MC) EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer, and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP. Methods: Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade Ⅳ bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP. The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation. The release of bone pain and the improvement of life quality were observed. Results: Bone pain of the patients was significantly alleviated to grade Ⅱ for 3-4 weeks after internal 153Sm-EDTMP irradiation. The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical. After injection of 0.65 × 37 MBq/kg 153Sm-EDTMP, the highest absorption dose in bone lesions was about 4.9-5.9 Gy, and the dose in the lesion margin was about 2.0 Gy. Using the highest dose as reference dose point, the relative absorption dose values of bone marrow, vertebra and sex organ near lesions were 0.48-1.1 Gy, 0.51-0.85 Gy, and 0.01-0.14 Gy, respectively. Conclusion: The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP. The painkilling effect is limited and in accordance with clinical observation.     

153Sm-EDTMP治疗多发骨转移瘤的剂量效应关系初步观察

背景与目的:核素内照射治疗的剂量计算一直是核医学研究的热点和难点之一,用蒙特卡罗法(MonteCarlo,MC)计算153Sm-乙二胺四甲撑膦酸(Samarium-153ethylenediaminetetramethylenephosphonicacid,153Sm-EDTMP)治疗多发性骨转移患者骨转移灶、骨髓等靶器官的吸收剂量,初步探讨病灶吸收剂量与153Sm-EDTMP止痛疗效的关系。方法:选择鼻咽癌、乳腺癌伴全身多发骨转移患者4例,患者骨痛剧烈,骨痛评分Ⅳ级,按0.65×37MBq/kg药量静脉注射,行153Sm-EDTMP内照射治疗。基于患者的时序性SPECT/CT扫描和累积尿液的放射性强度测定,确定患者的药物代谢动力学特点,利用MCEGS4程序计算骨转移灶和其它靶器官的吸收剂量及其分布。观察骨痛症状的缓解状况和生活质量的改善情况。结果:153Sm-EDTMP治疗后,患者骨痛明显减轻,骨痛评分达Ⅱ级,持续3～4周。骨转移灶和其它靶器官的三维吸收剂量分布图显示:病灶内剂量分布不均匀。骨转移灶的最高吸收剂量约为4.9～5.9Gy,病灶边缘的吸收剂量为2.0Gy左右,以病灶区最高剂量为参考点,则骨髓剂量为0.48～1.1Gy,骨皮质剂量为0.51～0.85Gy;病灶周围软组织的吸收剂量为0.01～0.14Gy。结论:按常规单次153Sm-EDTMP治疗,骨转移病灶远未达到30Gy姑息剂量水平,虽有一定的止痛结果,但止痛持续时间短,疗效有限,与临床观察结果一致。     

Safety analysis of repeated high doses of samarium-153 lexidronam in men with hormone-naive prostate cancer metastatic to bone

PURPOSE: The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone. PATIENTS AND METHODS: Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses. RESULTS: There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities. CONCLUSION: In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.     

153Sm-EDTMP治疗多发骨转移瘤的剂量效应关系初步观察

Objective： To calculate the focus absorption dose of ^153Sm-EDTMP with the Monte Carlo （MC） EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer, and investigate the relationship between the focus absorption dose and painkilling effect of ^153Sm-EDTMP. Methods： Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade IV bone pain were treated with radionuclide internal irradiation of ^153Sm-EDTMP. The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation. The release of bone pain and the improvement of life quality were observed. Results： Bone pain of the patients was significantly alleviated to grade II for 3-4 weeks after internal ^153Sm-EDTMP irradiation. The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical. After injection of 0.65 × 37 MBq/kg ^153Sm-EDTMP, the highest absorption dose in bone lesions was about 4.9-5.9 Gy, and the dose in the lesion margin was about 2.0 Gy. Using the highest dose as reference dose point, the relative absorption dose values of bone marrow, vertebra and sex organ near lesions were 0.48-1.1 Gy, 0.51-0.85 Gy, and 0.01-0.14 Gy, respectively. Conclusion： The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of ^153Sm-EDTMP. The painkilling effect is limited and in accordance with clinical observation.     

Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma

Radiation therapy can be an effective means to treat bone metastases, which occur in more than 50% of cancer patients. (153)Samarium lexidronam ((153)Sm-EDTMP; Quadramet, Cytogen) is a radiopharmaceutical designed for deposition into bone metastases. Bone scans can identify patients that may benefit from targeted radiation therapy with (153)Sm-EDTMP. As an unsealed source of radiation therapy, (153)Sm-EDTMP is simple to administer: 1 mCi/kg is given in a similar fashion to a bone scan injection ((99m)Tc-MDP bone scan injection is given at 0.2-0.35 mCi/kg. Therefore, both are administered intravenously. However, the radiation-absorbed dose and radiopharmaceutical energy are different). Nevertheless, despite simplicity of administration, (153)Sm-EDTMP is underutilized for improving cancer pain in the skeleton. Repeated cycles and combined treatment with other modalities such as bisphosphonates, chemotherapy and/or external beam radiation are possible. (153)Sm-EDTMP combined with bisphosphonates, chemotherapy and/or radiation may provide better palliation of bone metastases and also in bone-forming tumors (osteosarcoma). Encouraging experience using high-dose (153)Sm-EDTMP for total marrow irradiation in hematologic malignancies involving the bones (e.g., myeloma or acute leukemia) is also reviewed.     

153钐-乙二胺四亚甲基膦酸治疗骨转移瘤的疗效观察

目的：观察^153钐-乙二胺四亚甲基膦酸（^153钐-EDTMP）治疗骨转移瘤的疗效。方法：对96例骨转移瘤患者给予剂量范围为18．5～55．5MBq／kg的^153钐-EDTMP治疗。结果：患者疼痛总缓解率为86．5％（83／96）；影像学显示部分患者骨转移灶缩小、消失、减少或病灶处浓聚减弱。不良反应主要为骨髓抑制，经治疗2周～4周内皆能好转恢复。结论：^153钐-EDTMP对转移性骨肿瘤有明显缓解骨痛、控制病情进展的作用，使用安全。     

Bone invasion by Walker 256 carcinoma, line A in young and adult rats: effects of etidronate

Line A of Walker 256 carcinoma implanted in the muscle adjacent to the tibia of young (6 weeks) and adult (9 months) male rats invaded the bone. Osteolysis and reactive growth were greater in the bone of young animals than in adults. Ethane-1-hydroxy-1, 1-bisphosphonate prevented bone lysis and tumor invasion of the cortex both in young and adult animals. This model may be useful for studies of age-related differences in tumor infiltration into the bone and for investigating drug effects on this process.     

Walker 256/B malignant breast cancer cells improve femur angioarchitecture and disrupt hematological parameters in a rat model of tumor osteolysis

This study was designed to assess femur angioarchitecture and hematological effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor osteolysis was induced by in situ inoculation of Walker 256/B malignant cells. Six other rats were sham operated and served as control. Twenty days later, rats were euthanized, and femurs were collected than radiographed. Angioarchitecture [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2 different positions (P1: diaphysis, and P2: metaphysis) of the operated femora. Some hematological parameters were also assessed. Walker 256/B induced marked tumor osteolysis, with cortical perforation and trabecular destruction, associated increase in bone vascularization (increases of VNb and VV and decrease of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD and lower WTh. These effects were more prominent in P2. When compared to Sham group, significantly decreases at levels of red blood cell (RBC), hemoglobin (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats. These results suggest that Walker 256/B cells induced tumor osteolysis, improve hypervasculature especially near the tumoral foci (P2) associated hematological disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and disorganized morphology.