转移癌性骨痛^153Sm—EDTMP姑息治疗无效病例分析

目的：分析１５３ＳｍＥＤＴＭＰ 治疗转移癌性骨痛的无效病例,以探讨影响治疗效果的可能因素。材料与方法：从３０个月内收集的１２４ 例中,比较有效及无效组的病种、治疗方法、临床情况、年龄、性别等因素,以ＳＡＳ 软件进行成组与多因素分析。结果：治疗无效的２２ 例中男性占９１ ％ （２０ 例） ,肺癌比重大（１３ 例） ,患者的临床情况、治疗方法、全组年龄分布等与治疗效果无明确关系;肿瘤类型和性别与治疗效果相关; 肺癌组的性别和年龄与治疗效果相关。结论：１５３ＳｍＥＤＴＭＰ 治疗时,肺癌,男性,和相对年轻者可能效果差。尽管机制不详,了解这些因素有助于估计疗效。     

^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。     

153Sm-EDTMP致血液学毒性的多因素分析

目的 探讨^153Sm-乙二胺四甲撑膦酸（^153Sm-EDTMP）治疗导致白细胞、血小板降低发生的相关因素。方法 回顾性地整理206例^153Sm-EDTMP治疗后患者的资料，运用Logistic回归对数据进行单因素和多因素分析，对有意义的指标进行分析。结果 单因素分析结果表明：^153Sm-EDTMP治疗后，血液学毒性的发生与患者的年龄、骨转移灶数目、治疗前化疗史、同时进行外放疗、治疗次数有关；多因素分析结果显示，治疗前化疗史、同时进行外放疗、治疗次数等因素与血液学毒性产生与否有关；治疗前靠药物维持正常血象者也易出现血液学毒性。结论 ^153Sm-EDTMP治疗后血液学毒性的发生与几个因素有关，对有这些因素的患者，应特别注意治疗后血象的变化。     

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89SrCl2治疗组和153Sm-EDTMP治疗组,分别为69例和51例,89SrCl2剂量为1.11～2.22 MBq/Kg,153Sm-EDTMP剂量为25.9～37.0 MBq/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(X2=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(X2=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(X2=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.     

153Sm-EDTMP治疗多发性骨转移癌的临床观察

目的 评价放射性核素^153Sm-2乙二胺四甲基膦酸（^153Sm-EDTMP）治疗骨转移癌的疗效及其对造血功能的影响。方法 静脉注射^153Sm-EDTMP，每次0．5-1．5mCi／kg体重。观察治疗前、后患者的生活质量、病灶及血细胞的变化。结果 患者疼痛完全缓解率（CR）32．5％（13／40）；部分缓解率（PR）50％（20／40）；疾病进展（PD）17．5％（7／40）；总有效率82．5％。单一应用^153Sm-EDTMP，剂量≤1mCi的患者。对造血功能影响较小，一般于治疗后4周基本恢复。剂量〉1mCi或与化疗联合应用的患者，对造血功能影响较大，需用G-CSF或输血（包括脐血）治疗，约治疗后6周才能恢复。结论 ①^153Sm-EDTMP是比较理想的治疗多发性骨转移癌的放射性核素之一，具有控制病情发展、消除骨转移灶，改善患者生活质量的作用；②^153Sm-EDTMP治疗后可使患者血象一过性降低。剂量〉1mCi，连续治疗2次以上者可诱发全血减少；③脐血有恢复射线所致的造血功能损伤的作用。     

骨转移癌治疗药物^153SmEDTMP辐射剂量研究

^153Rm-EDTMP(乙二胺甲甲撑膦酸）是一种可望用于骨转移癌缓解治疗的放射性药物，注入示踪量^153Sm-EDTMP，准确计算离红骨髓的吸收剂量，是建立安全，有效的骨转移癌治疗方案的重要组成部分，本介绍了计算吸收剂量的一般原理和方法，并综述了近期在^153Sm-EDTMP辐射剂量及其效应方面的研究进展。     

153Sm-羟乙基乙二胺三甲撑膦酸(HEDTMP)的动物实验研究

目的：初步探讨^153Sm-羧乙基乙二胺三甲撑膦酸（HEDTMP）的生物学性能。方法：分别以^99Tc^m-亚甲基二膦酸盐（MDP）和^153Sm-乙二胺四甲基膦酸（EDTMP）作对照，进行^153Sm-HEDTMP新西兰兔、Wistar大鼠骨显像和昆明小白鼠体内分布实验。结果：①^153Sm-HEDTMP动物骨显像提示有较高的骨摄取，颅骨、脊柱、四肢显示清晰，与^99Tc^m-MDP及^153Sm-EDTMP的骨显像效果相似。②^153Sm-HEDTMP有快速的血清除与骨摄取，注射后330min骨摄取为19.13％ID/g，3h为24.54％ID/g，24h为18.95％ID/g；示踪剂主要经肾脏排泄，非靶脏器放射性残留低。③^153Sm-HEDTMP的骨摄取和靶/非靶比值比^153Sm-EDTMP高。结论：^153Sm-HEDTMP显示出良好的生物学性能，有解雇成为新的放射性骨治疗剂。     

~(153)Sm-EDTMP治疗多发性骨转移癌

恶性肿瘤发生骨转移,出现骨痛、病理性骨折,严重影响患者的生活质量.我们用153Sm-EDTMP治疗多发性骨转移癌65例,疗效明显,现报告如下.     

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.     

^153Sm—EDTMP显像测定骨摄取率在个体化治疗剂量计算中的应用

目的 探讨^153Sm-乙二胺四甲撑膦酸（EDTMP）全身显像法在个体化给药剂量计算中的价值。方法 对20例骨转移癌患者进行^153Sm-EDTMP显像,计算骨摄取率,并与尿液收集法进行比较。结果 显像法与尿液收集法所测得的骨摄取率之间具有很好的相关性（r=0.93)。根据显像法计算的骨摄取率,给药剂量为1．40－2．27GBq(平均1．90GBq),骨髓吸收剂量为1．37－1．43Gy(平均1．40Gy)。按标准体重计算,则应给予的剂量为1．75－2．41GBq（平均2．18GBq),骨髓吸收剂量为1．37－2．27Gy(平均1．63Gy)。两种方法给药剂量之间差异有显著性（t=4.075,P=0.001),同髓吸收剂量差异也有显著性（t=4.030,P=0.001)。结论 骨转移癌患者治疗剂量按^153Sm-EDTMP显像法测定的骨摄取率进行个体化给药,在达到治疗目的同时,还可避免发生骨髓毒性反应,具有重要的临床价值。     

153Sm]EDTMP: a potential therapy for bone cancer pain.

Reactor-produced samarium-153 (153Sm) is both a beta and gamma emitter with a physical half-life of 46.3 hours. When complexed with EDTMP, more than 50% of the administered dose localizes in bone. A therapeutic trial on patients with painful bone metastases performed at the University of Missouri produced relief in 65.4% of the patients who were evaluable. Myelotoxicity was mild and transient. For [153Sm]EDTMP to attain clinical utility, studies demonstrating its efficacy as an analgesic must be performed to exclude a "ligand analgesic effect".     

Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China

A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with ¹⁵³Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician’s Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29±14.47 and 20.13±13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54±25.90 to 71.67±26.53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5×10⁹/l) and platelet (nadir 6.0×10¹⁰/l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, ¹⁵³Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of treatment. Received 4 July and in revised form 6 September 1998     

Clinical role of Sm-153 EDTMP in the treatment of painful bone metastatic disease

PURPOSE: Sm-153 EDTMP is an effective treatment of painful bone metastases from different neoplasms. However, there are few studies describing clinical experience with this therapeutic modality. The aim of this clinical study was to evaluate the efficacy of Sm-153 EDTMP in a group of patients with skeletal metastases and poor pain control with conventional therapies. MATERIALS AND METHODS: Sixty-four patients with painful bone metastases treated with Sm-153 EDTMP were retrospectively evaluated. Nine patients were treated twice. The most common primaries were breast in 28 cases (44%) and prostate in 27 (41%). Treatment efficacy was assessed by a visual analog scale, analgesic consumption, and performance status before and after treatment. Response was graded as complete, moderate, or minor. Toxicity evaluation included analytic parameters (blood counts, renal function) and clinical follow up. RESULTS: Efficacy and toxicity were evaluated separately for each dose (total doses: 73), and complete follow up was only possible in 62 of 73 administrations. The response rate was 85% (21% complete, 40% moderate, and 24% minor). Onset of improvement took place a median of 7 days after Sm-153 EDTMP administration, and pain relief persisted for a mean of 3 months. No relevant toxicity was found in the early phase. Myelotoxicity appeared in 29% of the administrations and was mild in most cases (there was one case of grade 4 leukopenia). CONCLUSIONS: Sm-153 EDTMP is a good therapeutic option for patients with painful bone metastases. It is an effective treatment of pain relief without major secondary effects.     

~(153)Sm-EDTMP治疗骨转移癌疼痛的现状

以往骨转移癌病人疼痛治疗的常用方法是放疗和阶梯性使用止痛药物。随着核医学的发展 ,亲骨性放射性核素越来越多地用于癌症的治疗 ,尤其是骨转移癌的止痛治疗。其中 ,1 5 3　 Sm- EDTMP(1 5 3　 Sm-乙二胺四甲撑膦酸 )在缓解疼痛 ,改善生活质量 ,减少新的骨转移病灶发生 ,及降低治疗费用等方面都有很大优势     

153Sm-EDTMP-纳米羟基磷灰石的生物学性能

目的研究^153Sm-乙二胺四甲撑膦酸(EDTMP)-纳米羟基磷灰石(HA)的体内外生物学性能。方法采用溶胶-凝胶法合成纳米HA并用电镜和X线衍射进行鉴定，采用独立变数法研究^153Sm-EDTMP-纳米HA的最佳标记条件并对产物进行体外稳定性分析，进行^153Sm-EDTMP-纳米HA新西兰兔显像，比较纳米HA、^153Sm-EDTMP和^153Sm-EDTMP-纳米HA对肝癌SMMC-7721和乳腺癌MCF-7细胞的体外抑制作用。结果①纳米HA为针状结晶，结晶度较好，径向10～30nm，轴向70～100nm，X线衍射证明产物为HA。②^153Sm-EDTMP-纳米HA的标记率均在95％以上。体外稳定性好，在生理盐水中放置48h后放化纯仍大于95％。③正常新西兰兔^153Sm-EDTMP-纳米HA显像对比度较好，骨骼系统显示清晰，肾脏显影，血清中放射性下降较快。④^153Sm-EDTMP-纳米HA对肝癌SMMC-7721和乳腺癌MCF-7细胞的半抑制率质量浓度分别为1．98mg／L和0．075mg／L，而纳米HA分别为3．31mg／L和0．52mg／L，^153Sm-EDTMP分别为4．32mg／L和0．67mg／L，^153Sm-EDTMP-纳米HA对肿瘤生长的抑制率明显高于纳米HA和^153Sm-EDTMP。结论^153Sm-EDTMP-纳米HA的骨组织摄取好，有明显的体外抑制肿瘤生长的作用。     

153Sm-EDTMP for bone pain palliation in skeletal metastases

153Sm-ethylene diamine tetramethylene phosphonate (EDTMP) is a widely available and extensively tested radiopharmaceutical for systemic radionuclide therapy in patients with symptomatic multiple skeletal metastases. Its use is approved for any secondary bone lesion which has been shown to accumulate (99m)Tc-methylene diphosphonate, including breast carcinoma. The molecule is stable in vitro and upon injection more than 50% of the dose is avidly fixed by lesional and non-lesional bone, with the rest being rapidly eliminated unchanged via the urine. The short half-life (46.3 h), the relatively low-energy beta emissions (E(ave)=233 keV) and the gamma emission (103 keV) make (153)Sm a very attractive radionuclide, allowing therapeutic delivery of short-range electrons at relatively high dose rates with external imaging to corroborate biodistribution and possible dosimetric estimates. For a standard dose of 2,590 MBq/70 kg, the estimated radiation dose to metastases is 86.5 Gy. Critical organs are the bladder wall (2.5 Gy/2,590 MBq) and red marrow (4 Gy/2,590 MBq), with the latter being the critical factor in clinical practice as the dose-limiting factor is marrow radiotoxicity. The therapy has, however, proved safe provided that the platelet count exceeds 100 x 10(9)/l and the white blood cell count exceeds 3.5 x 10(9)/l. Clinical data obtained in fewer than 250 patients, within several studies, lead to the following conclusions: a dose of 37 MBq/kg has a better therapeutic ratio than a dose of 18.5 MBq/kg; the mean pain palliation rate after a single treatment in breast cancer is about 80%; toxicity is generally mild and transitory; and re-treatments are effective and safe provided that haematological values have fully recovered.     

An individual dosimetric approach to 153Sm-EDTMP therapy for pain palliation in bone metastases in correlation with clinical results

BACKGROUND: The clinical results of therapy using 153Sm ethylenediamine-N,N,N'N'-tetrakis(methylene phosphonic acid) (153Sm-EDTMP) were correlated with radiation dose indices in metastases, with the intention of improving the therapeutic efficacy. METHODS: Fifty-six patients with disseminated bone metastases were treated. Prior to therapy, whole-body scans and single photon emission computed tomography (SPECT) of the trunk were performed. Whole-body retention of 99mTc labelled phosphonates was compared with 153Sm-EDTMP retention after therapy. Estimations of the volumes of bone lesions were done by SPECT. Assuming a solid tumour but a thin metabolically active boundary zone between tumour and healthy bone that absorbed the beta radiation, we estimated an 'irradiated volume' by using a spherical shell model of 6 mm thickness. Local tracer uptake in lesions was assessed by regions of interest techniques on conjugated views of whole-body scans with homogeneous attenuation correction. Calculation of the dose index by applying the Medical Internal Radiation Dosimetry (MIRD) scheme was done retrospectively in 10 patients and prospectively in 22 cases. Depending on changes in pain/mobility scores, results were classified as 'very good', 'good' and 'no response'. RESULTS: A mean dose index > or =10 per lesion was estimated under the condition of a homogeneous uptake within the idealized, spherical, tumour volume. Assuming that the uptake of the radiopharmaceutical occurs mostly within an outer shell of the tumour, dose indices to this 'irradiated volume' can increase to more than twice that value. CONCLUSION: Very good clinical results for bone pain palliation by using 153Sm-EDTMP therapy could be found in patients receiving a dose index >15 per lesion. Even this approximate dosimetric approach, considering the individual differences in tumour spread and the varying intensity of 153Sm uptake, could improve the impact of 153Sm-EDTMP for pain control in cancer patients.     

Radiation dose calculations in persons receiving injection of samarium-153 EDTMP

Samarium-153 EDTMP has been proposed as a radionuclide therapeutic agent to treat malignant bone tissue disorders. Data obtained from laboratory rats has been used to calculate the radiation dose for humans following the administration of [153Sm]EDTMP. The data reveals that the highest doses are present in the skeleton and the urinary bladder wall (bladder dose varies with frequency of voiding). Skeletal activity was used to estimate the bone marrow dose from the [153Sm]EDTMP beta radiation. Although this estimate indicates high marrow irradiation it is only an approximation since the beta radiation from inhomogeneously deposited bone activity surrounding the marrow produces variable radiation dose distributions.     

Human pharmacokinetics of samarium-153 EDTMP in metastatic cancer

Samarium-153 ethylenediaminetetramethylene phosphonic acid ([153Sm]EDTMP) has been proposed to palliate pain resulting from osteoblastic metastatic bone cancer. Encouraging results in dogs with primary malignant bone cancer provided the catalysis for human biodistribution studies in five patients with metastatic skeletal carcinoma. The objective was to assess the preferential localization of [153Sm]EDTMP in bony lesions and compare it to the 99mTc-labeled phosphonates. Blood clearance of [153Sm]EDTMP was rapid with minimal accumulation in nonosseous tissues. Both radiopharmaceuticals showed identical lesion uptake in 23 paired lesions (p greater than 0.05). This indicates that the two radiopharmaceuticals concentrate in metastatic skeletal lesions by the same mechanism and since [153Sm]EDTMP emits beta radiation it may be therapeutically useful in ameliorating metastatic bony cancer pain.