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。     

髓母细胞瘤患者全脑全脊髓放疗的血液学毒性观察

目的了解全脑全脊髓放疗对髓母细胞瘤患者血象的影响,分析其危险因素。方法回顾性地分析30例髓母细胞瘤患者在接受全脑全脊髓放疗期间血象变化,按照下降程度分为正常与轻度抑制（0/Ⅰ/Ⅱ）和重度抑制（Ⅲ/Ⅳ）,分析性别、年龄、放疗累积剂量与血液学毒性的相关性。结果 96.7%（29/30）的患者出现白细胞减少,63.3%（19/30）的患者出现血小板减少,70%的患者在放疗开始2周内出现白细胞减少,放疗的累积剂量与血液学毒性有关（P〈0.001）。结论大部分患者在前两周出现白细胞减少,放疗累积剂量（Dt）0～18 Gy出现血液学毒性的患者中发生重度抑制的白细胞血液学毒性的比例更高,放疗开始2周内出现白细胞减少比例高,应密切观察血象变化,发生血液学毒性时应及时处理。     

髓母细胞瘤患者全脑全脊髓放疗的血液学毒性观察

目的了解全脑全脊髓放疗对髓母细胞瘤患者血象的影响,分析其危险因素。方法回顾性地分析30例髓母细胞瘤患者在接受全脑全脊髓放疗期间血象变化,按照下降程度分为正常与轻度抑制(0/Ⅰ/Ⅱ)和重度抑制(Ⅲ/Ⅳ),分析性别、年龄、放疗累积剂量与血液学毒性的相关性。结果 96.7%(29/30)的患者出现白细胞减少,63.3%(19/30)的患者出现血小板减少,70%的患者在放疗开始2周内出现白细胞减少,放疗的累积剂量与血液学毒性有关(P<0.001)。结论大部分患者在前两周出现白细胞减少,放疗累积剂量(Dt)0～18 Gy出现血液学毒性的患者中发生重度抑制的白细胞血液学毒性的比例更高,放疗开始2周内出现白细胞减少比例高,应密切观察血象变化,发生血液学毒性时应及时处理。     

^153Sm—EDTMP：有效地治疗骨癌疼痛

^153Sm-EDTMP试用于转移性骨癌疼痛病人的治疗，估计65.4%的病人疼痛可得到缓解，且只有轻度和短暂的骨髓毒性，为使^153Sm-EDTMP获得临床应用，必须进一步研究证明其作为止痛剂的功效，以排除“配体止痛作用”。     

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。     

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-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。     

^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。     

乳腺癌放、化疗致放射性肺炎与相关因素分析

目的 观察乳腺癌放疗的患者使用化疗药物及其他因素与放射性肺炎发生率的关系。方法 采用回顾性85例术后辅助放、化疗的乳腺癌患者放疗的照射剂量，使用化疗药物的时间、种类、患者的年龄和肺部疾病与放射性肺炎发生率的关系。结果 临床有放射性肺炎症状者5例，其中1例需要积极治疗；有影像学改变的放射性肺炎共16例，为18．8％，与放疗剂量、化疗时间、药物种类和肺部疾病史有关。结论 照射剂量、放疗后化疗、肺部原有疾病增加了放射性肺炎的发生率。     

局部放疗联合89Sr治疗骨转移癌的疗效观察

目的评价局部放疗配合放射性核素^89Sr治疗骨转移癌的疗放，分析单纯放疗单纯核素^89Sr治疗及联合治疗的副作用。方法观察60例确诊为骨转移癌的患者，分为3组，每组20例。局部放疗（A组），采用6MV直线加速器外照射给予吸收剂量30—60Gy，2—4周，局部放疗＋^89Sr治疗（B组），单纯^89Sr治疗（C组）放射性核素^89Sr静脉内注射3—4mCi。结果治疗后B组骨痛缓解，原发灶改善明显好于A、C组；新增疼痛部位及转移灶均少于A、C组（P〈0．05）。治疗后血液学的毒性3组差异统计学意义（P〉0．05）。结论局部放疗配合^89Sr治疗骨转移癌有较好的疗效，提示对单发性骨转移患者的压痛明显部位给予局部外照射止痛效果明显，对多发骨转移且病灶相距较近的给予放疗联合^89Sr治疗效果安全可靠，对全身性多发性骨转移者采用单纯放射性核素^89Sr治疗对于止痛和控制骨转移有一定疗效。     

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.     

Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

INTRODUCTION: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate (153 Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic 153 Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of 153 Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of 153 Sm-EDTMP on growth of long bones. METHODS: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of 153 Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P<.05. RESULTS: Significant differences in lengths of multiple bones were detected between the high-dose group and other treatment groups and controls at each time interval. A significant difference in lengths of the tibias was also noted in the medium-treatment group, compared to controls. Mean reduction of bone length was first detected at 4 months and did not increase significantly over time. CONCLUSIONS: These data suggest that clinically significant bone shortening may occur as a result of high-dosage administration of 153 Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted.     

Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.

Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. When chelated to ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in vitro and in vivo. In this study, we administered escalating amounts of 153Sm-EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful metastatic bone cancer. A complete concordance was found when the scintigrams of 153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r = 0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30 min following injection (r = -0.79; p = 0.0001) and was unaffected by the administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia occurred in patients who had low pretreatment platelet counts, albeit within the normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective. Our preliminary results indicate that 153Sm-EDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain, and further study is necessary to ascertain its optimal dose, efficacy and toxicity.     

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.     

Samarium-153 EDTMP therapy of disseminated skeletal metastasis

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.     

Bone uptake studies in rabbits before and after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP.

The aim of this animal study was to measure the bone uptake of (99m)Tc-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with (153)Sm-ethylenediaminetetramethylenephosphonate (EDTMP) or (186)Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. METHODS: Quantitative bone scanning using 100 MBq (99m)Tc-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either (153)Sm-EDTMP or (186)Re-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. RESULTS: In animals treated with (153)Sm-EDTMP (n = 6), no differences could be proven for the bone uptake of (99m)Tc-HDP at 24 h after injection before and after therapy (51.1% +/- 5.5% vs. 48.0% +/- 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with (186)Re-HEDP: Bone uptake (44.8% +/- 6.7% vs. 40.4% +/- 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. CONCLUSION: No significant impairment of bone uptake of (99m)Tc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for (186)Re-HEDP and (153)Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifiable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2-3 mo after standard treatment with (186)Re-HEDP or (153)Sm-EDTMP.     

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     

Intraorgan biodistribution and dosimetry of 153Sm-ethylenediaminetetramethylene phosphonate in juvenile rabbit tibia: implications for targeted radiotherapy of osteosarcoma.

Targeted radiotherapy using 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) is currently under investigation for treatment of primary osteosarcoma. Human osteosarcoma most frequently occurs in skeletally immature individuals, and previous studies in a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage might occur as a result of systemic 153Sm-EDTMP therapy. The aim of this study was to determine the distribution of 153Sm-EDTMP within the tibias of juvenile rabbits and estimate the radiation-absorbed doses delivered to the physeal cartilage. METHODS: Eight-week-old New Zealand White rabbits were injected intravenously with 7.57 kBq (280 microCi) of 153Sm-EDTMP. At 21 h after injection, the biodistribution of 153Sm in the epiphysis, metaphysis, diaphysis, and red marrow of the tibia was obtained. Two-dimensional digital autoradiography was performed on 2-mm sections of tibias for qualitative comparison with the biodistribution data. Self-tissue and cross-tissue absorbed doses were calculated using absorbed fractions generated by the Monte Carlo particle transport code MCNP-4C. RESULTS: The highest uptakes (percentage injected dose per gram [%ID/g] of tissue) of 153Sm, 1.99-2.56 %ID/g, were found in the proximal and distal metaphyses, 70%-73% of which localized within 3 mm of the physeal cartilage. The second highest tissues of uptake were the proximal and distal epiphyses, at 0.33-0.62%ID/g. Digital autoradiography imaging confirmed that the majority of 153Sm deposited in the tibia localized to these tissues. Radiation-absorbed doses to the proximal and distal metaphyses were 183 and 130 mGy/MBq, respectively, and those to the proximal and distal epiphyses were 141 and 43.4 mGy/MBq, respectively. These tissues represented the only source compartments contributing to the physeal cartilage doses of 50.0 mGy/MBq for the proximal physis and 39.2 mGy/MBq for the distal physis. CONCLUSION: The 153Sm absorbed doses to the physeal cartilage were consistent with values that can cause dose-limiting damage to rapidly proliferating and differentiating chondrocytes. The pronounced uptake in the juvenile epiphysis indicates that the proliferating zone of the physis can be irradiated from multiple areas, which could increase the expression and degree of radiation damage. Further investigation of the effects of 153Sm-EDTMP on immature physeal cartilage is warranted to develop optimized treatment regimens.     

Safety and feasibility of percutaneous vertebroplasty with radioactive (153)Sm PMMA in an animal model

Purpose

We investigated the safety and feasibility of the combination of samarium-153-ethylenediamine tetramethylene phosphonate (¹⁵³Sm-EDTMP)-incorporated bone cement (BC) with percutaneous vertebroplasty (PVP) in dogs.

Methods and materials

¹⁵³Sm-EDTMP-incorporated BC was prepared by combining solid ¹⁵³Sm-EDTMP and polymethylmethacrylate (PMMA) immediately before PVP. It was then injected into the vertebrae of four healthy mongrel dogs (two males and two females) by PVP under CT guidance. Each dog was subjected to five PVP sessions at a ¹⁵³Sm-EDTMP dose of 30-70 mCi. The suppressive effect of local injection of ¹⁵³Sm-EDTMP on the hematopoietic system was evaluated through counting of peripheral blood cells. Distribution of ¹⁵³Sm-EDTMP-incorporated BC and the status of tissues adjacent to injected vertebrae were evaluated with SPECT, CT and MRI. Histopathology was carried out to assess the influence of PVP on the vertebra and adjacent tissues at the microscopic level.

Results

PVP was done successfully, and all dogs exhibited normal behavior and stable physical signs after procedures. ¹⁵³Sm-EDTMP-incorporated BC was concentrated mainly in target vertebrae, and the peripheral blood cells remained within normal range. The spinal cord and tissues around BC did not exhibit signs of injury even when the dosage of ¹⁵³Sm-EDTMP increased from 30 mCi to 70 mCi.

Conclusion

A dose lower than 70 mCi of ¹⁵³Sm is safe when it was injected into vertebrae. ¹⁵³Sm-EDTMP-incorporated BC did not influence the effect of PVP. This means might strengthen anti-tumor activity locally for vertebra with osseous metastasis without damaging adjacent tissues.     

Samarium — 153 EDTMP therapy of disseminated skeletal metastasis

¹⁵³Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of ¹⁵³Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of ¹⁵³Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with ¹⁵³Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of ¹⁵³Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of ¹⁵³Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of ¹⁵³Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed ¹⁵³Sm-EDTMP-induced myclotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.