^153钐-乙二胺四甲撑膦酸治疗肺癌、乳腺癌及前列腺癌骨转移166例的临床疗效

目的研究^153钐-乙二胺四甲撑膦酸（^153Sm-EDTMP）治疗肺癌、乳腺癌及前列腺癌骨转移所致骨痛的疗效。方法静脉注射^153Sm—EDTMP，给药剂量18．5～37．0MBq／kg（0．5～1．0mCi／kg）体重，每隔1～2个月注射1次。结果^153Sm—EDTMP治疗肺癌、乳腺癌及前列腺癌骨转移所致骨痛的总有效率分别为68．5％、89．3％及100％，且乳腺癌和前列腺癌的疗效与肺癌相比有统计学意义（P〈0．05），81．5％患者白细胞或血小板计数一过性减少。结论放射性核素治疗以成骨为主的骨转移灶，止痛效果明显，方法简便，不良反应小。     

二氯化锶治疗恶性肿瘤骨转移疗效观察

目的探索二氯化锶（^89SrCl）治疗多发性骨转移癌的疗效。方法对126例恶性肿瘤骨转移伴骨痛的患者,静脉注射^89SrCl后,观察其镇痛作用、不良反应及对骨转移病灶的影响。结果治疗后109例骨痛消失或缓解（总有效率86．5%）,38例患者骨转移病灶缩小或消失（总有效率30．2％）;少数（19例）病人出现白细胞一过性减低,肝、肾功能无变化。结论^89SrCl对恶性肿瘤骨转移导致的骨痛、骨破坏有较好的疗效,副作用小,可重复用药。     

帕米膦酸二钠联合153Sm-EDTMP治疗多发性骨转移瘤28例

目的：观察帕米膦酸二钠联合^153钐-乙二胺四甲撑膦酸（^153Sm—EDTMP）治疗多发性骨转移瘤的疗效及毒副作用。方法：53例多发性骨转移瘤患者前瞻性随机分为帕米膦酸二钠联合^153Sm—EDTMP治疗组（治疗组）和单用帕米膦酸二钠治疗组（对照组），观察疗效及毒性反应。结果：治疗组和对照组的止痛有效率分别为82.1％和76．0％（P〉0．05），骨转移影像缓解率分别为46．4％和20．0％（P〈0．05），毒副作用差异元显著性。结论：帕米膦酸二钠联合^153Sm—EDTMP治疗多发性骨转移瘤近期疗效好、毒副作用小。     

^153钐—乙二胺四亚甲基膦酸治疗112例骨转移癌的临床观察

目的：观察^153^153钐－乙二胺四亚甲基膦酸（^153Sm-EDTMP)治疗恶性肿瘤骨转移癌的临床疗效。方法：按照治疗适应证，对112例经病理证实的恶性肿瘤发生骨转移癌患者者进行一次单剂量^153Sm-EDTMP治疗，观察治疗后1周－8周的疗效及不良反应，治疗后1周、2周、4周复查血像；1周、4周、8周复查血清碱性磷酸酶（ALP）；4周复查骨显像。结果：疼痛完全缓解者占39．3％（44／112），部分缓解者占42．85（48／112），总有效率达82．1％（92／112）；ALP有59．8％（67／112）患者在治疗前异常升高，经治疗后异常组中有86．6％（58／67），患者ALP出现明显下降；骨显像半定量分析显示有40．2％（45／112）患者骨转移病灶消失、缩小、减少或病灶处浓聚减弱。不良反应主要为骨髓抑制，经治疗2－4周内皆能恢复。结论^153Sm-EDTMP治疗骨转移癌疗效好、副反应少，使用安全，能有效改善虱生活质量。     

食管癌患者骨转移临床特点研究

目的研究核素全身骨显像探讨河南省食管癌患者骨转移的特点。方法对郑州大学附属肿瘤医院1187例术前河南籍食管癌患者全身骨显像进行了回顾性分析。结果1187例食管癌患者中,发生骨转移者185例,发生率为15．6％,其中单发骨转移占43．6％,多发骨转移占56．4％;椎体骨、胸肋锁骨、盆骨、四肢骨、其它骨转移者分别占骨转移患者的57．3％、42．1％、22．7％、19．4％、10．8％。骨转移患者核素骨显像表现为“热区”、“冷区”、“冷、热区”共存者分别为87．2％,4．5％,8．3％。结论河南省食管癌患者骨转移发生率较高、多见于胸椎转移、以成骨性表现为主,手术前有必要进行核素全身骨显像检查。     

云克与153钐-乙二胺四甲基膦酸对骨转移癌患者骨痛及疼痛因子的影响

目的：探讨云克（^99锝-亚甲基二膦酸盐注射液，^99Tc-MDP）与^153钐-乙二胺四甲基膦酸（^153Sm-EDTMP）对多发性骨转移癌患者骨痛反应与体内疼痛因子的变化的关系。方法：对93例多发性骨转移癌患者用云克与^153Sm-EDTMP治疗。其中单独^153Sm-EDTMP治疗组55例，单独云克治疗组及云克与^153Sm-EDTMP联合治疗组各19例。分别对其治疗前与治疗后（3个月后）血浆内皮素（ET）、降钙素基因相关肽（CGRP）、血栓素B2（TXB2）与6-酮-前列环素F1α（6-k-PGF1α）含量变化进行了测定。结果：治疗后三组患者骨痛缓解率分别为69．1％（38／55）、73．7％（14／19）及89．5％（17／19）。三组中，血浆ET与6-k-PGF1α含量治疗3月后均显著高于治疗前（P〈0．01）。血浆CGRP与TX＆含量治疗后与治疗前相比，^153Sm-EDTMP治疗组差异无统计学意义（P〉0．05）。云克治疗组及联合治疗组两组TXB，含量治疗后与治疗前相比，差异无统计学意义（P〉0．05）；而CGRP则显著降低（P〈0．05）。结论：云克与^153Sm-EDTMP联合治疗骨转移癌明显优于单独云克与单独^153Sm-EDTMP治疗；治疗后骨痛反应与疼痛因子ET、6-k-PGF1α及CGRP含量变化有关。     

全身骨显像诊断恶性肿瘤骨转移结果分析

对经病理学确诊为恶性肿瘤病人１９７例进行全身骨显像，检出骨转移８６例。骨转移灶的分布显示，鼻咽癌的肢体骨转移率与脊柱转移率桢，为２６％；肺癌的肢体骨转移率为２５．６％，胸部骨为２９．５％，脊柱为２３．１％，骨盆为１５．４％。说明肺癌和鼻咽癌的骨转移部分分布无明显规律。同期接受骨显像和Ｘ线摄片检查，两种结果均呈阳性者１２例，Ｘ线摄惩检出病灶１６个，骨显像检出病灶４２个。显然，骨显像诊断恶性肿瘤骨转移     

放射性核素全身骨显像中单发病灶的临床价值

目的探讨放射性核素全身骨显像中单发病灶的临床价值。方法受检者常规^99Tc^m—亚甲基二膦酸盐(MDP)骨显像．对310例骨显像中单发病灶进行临床分析。结果有肿瘤病史的256例患者。骨转移率为24．2％(62／256),无肿瘤病史的54例患者中。骨转移率为5．5％(3／54),两者差异有显著性;总骨转移率为20．9％(65／310)。其中前列腺癌20.8％(5／24),乳腺癌22.4％(17／76),肺癌32.7％(18/55),泌尿系肿瘤23．1(3/13）,消化系肿瘤16．7％(7／42),其他肿瘤26．1％(12／46),无肿瘤病史患者中．94．4％(51／54)的单发病灶主要是良性病灶。结论在骨显像单发病灶中．有原发肿瘤病史患者24．2％为早期骨转移灶．无原发肿瘤病史患者94．％主要为良性改变。初步得出了全身骨显像中单个病灶临床分析标准和价值。     

全身骨扫描在肺癌骨转移临床诊断中的应用价值

目的：探索全身骨扫描在肺癌骨转移临床诊断中的应用价值。方法：选取2020年9月—2021年10月信阳市中心医院收治的肺癌患者356例,入院后均开展^99mTc-MDP全身骨扫描检查。根据^99mTc-MDP骨扫描检查结果,分析不同病理类型肺癌骨转移数量分布(单发或多发)和部位分布(胸部、脊柱、骨盆、四肢、颅骨),比较不同TNM分期肺癌患者骨转移情况。结果：356例患者中骨转移139例,骨痛、神经系统症状、病理性骨折例数分别为60、18、2。骨转移单发28例,多发111例;腺癌、鳞状细胞癌、腺鳞癌、小细胞肺癌、复合性小细胞癌、未定型发生骨转移分别为78例、38例、7例、8例、6例、2例。139例骨转移患者共发现转移病灶386个,以胸部病灶最多(158个),其次为脊柱(127个)、骨盆(57个)、四肢(35个)及颅骨(9个)。T₄分期肺癌患者骨转移发生率为55.26%,高于T₁、T₂、T₃分期的24.59%、23.25%、15.79%,差异有统计学意义(P<...     

肺癌的全身骨显像表现

报告193例经病理证实的肺癌骨显像结果。其阳性率为74％（143／193）。肺癌的病理类型不同，骨转移的发生率也不同。腺癌、鳞癌较高，未分化癌较低（P＜0．01）。肺癌骨转移的部位也有明显差异，胸部、脊柱分别为50．2％及45．6％，骨盆、四肢为29％及30％，颅骨为10.4％。多发性骨转移为83．2％（119／143），单发病例为16．8％（24／143）。肺癌患者应做全身骨显像，这对分期、治疗和预后都十分重要。     

89锶内照射治疗前列腺癌相关骨痛的疗效观察

目的 探讨核素89锶(89Sr)内照射对前列腺癌骨转移疼痛的治疗效果和不良反应.方法 对18例明确诊断为前列腺癌骨转移伴有明显疼痛症状的患者采用双侧睾丸切除加氟他胺治疗后,均接受核素89Sr内照射治疗,观察治疗后的止痛疗效、PSA变化、不良反应.结果 经89Sr治疗后,总有效率为88.9%(16/18),骨转移病灶数量也明显减少,疼痛缓解率4～7 个月,PSA有不同程度下降,不良反应主要为轻度可逆性骨髓造血功能损害.结论 应用核素89Sr内照射治疗能明显缓解前列腺癌骨转移引起的疼痛,对前列腺癌骨转移灶亦有抑制生长作用.     

^89Sr治疗前列腺癌骨转移临床观察

目的评价放射性核素^89锶（^89Sr）在前列腺癌骨转移中的治疗效果和不良反应。方法观察前列腺癌骨转移并伴有不同程度骨痛患者66例,使用^89SrCl2静脉注射治疗,观察其镇痛效果、骨转移灶的变化、前列腺特异性抗原（PSA）及不良反应等。结果66例患者接受。^89Sr治疗后,止痛的总有效率达89．4％（59／66）,无效10．6％（7／66）,骨转移灶有明显减少。对PSA有不同程度的下降：所有治疗者均未发现严重的不良反应和毒副作用。结论^89Sr治疗前列腺癌骨转移疼痛效果明显,对前列腺癌骨转移灶亦有治疗作用,是一种安全有效的方法。     

~(89)Sr治疗前列腺癌骨转移临床观察

目的评价放射性核素89锶(89Sr)在前列腺癌骨转移中的治疗效果和不良反应。方法观察前列腺癌骨转移并伴有不同程度骨痛患者66例,使用89SrCl2静脉注射治疗,观察其镇痛效果、骨转移灶的变化、前列腺特异性抗原(PSA)及不良反应等。结果66例患者接受89Sr治疗后,止痛的总有效率达89.4%(59/66),无效10.6%(7/66),骨转移灶有明显减少。对PSA有不同程度的下降。所有治疗者均未发现严重的不良反应和毒副作用。结论89Sr治疗前列腺癌骨转移疼痛效果明显,对前列腺癌骨转移灶亦有治疗作用,是一种安全有效的方法。     

Syntheses and evaluation of 68Ga‐ and 153Sm‐labeled DOTA‐conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases

This article reports the syntheses and evaluation of ⁶⁸Ga‐ and ¹⁵³Sm‐complexes of a new DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid)‐conjugated geminal bisphosphonate, DOTA‐Bn‐SCN‐BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three‐step reaction scheme. Gallium‐68‐ and ¹⁵³Sm‐complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate‐buffered saline (PBS) and human serum. Both the complexes showed high affinity for hydroxyapatite particles in in vitro binding study. In biodistribution studies carried out in normal Wistar rats, both the complexes exhibited rapid skeletal accumulation with almost no retention in any other major organ. The newly synthesized molecule DOTA‐Bn‐SCN‐BP would therefore be a promising targeting ligand for the development of radiopharmaceuticals for both imaging skeletal metastases and palliation of pain arising out of it in patients with cancer when radiolabeled with ⁶⁸Ga and ¹⁵³Sm, respectively. A systematic comparative evaluation, however, showed that there was no significant improvement of skeletal accumulation of the ¹⁵³Sm‐DOTA‐Bn‐SCN‐BP complex over ¹⁵³Sm‐DOTMP (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethylenephosphonic acid) as the later itself demonstrated optimal properties required for an agent for bone pain palliation.     

Targeted radiotherapy of bone malignancies

The severe pain associated with many disorders affecting bone account for a large proportion of cases of patient morbidity, due to the encumbrance of mobility and therefore, compromised quality of life. Skeletal metastasis is one such condition, which generally complicates the treatment of the primary cancers such as that of the breast, prostate and lung - causing intense pain and eventually even mortality. This paper presents examples of various approaches explored and proposed in the ongoing search to identify better radiopharmaceuticals for the treatment of bone disorders such as metastases. The primary objective of these developments is to alleviate the debilitating pain commonly associated with bone lesions. The efficacy of a radiotherapeutic agent intended for the treatment of diseased bone is particularly dependent on the radiation dose to the tumor cells and on the extent to which suppression of bone marrow or other critical organs can be avoided. Therefore, the design rationale requires careful consideration of the choice radionuclide and especially ensuring that the drug selectively targets the lesion or tumor site. The options pursued include the use of radioisotopes with an intrinsic affinity for bone, such as (89)Sr or (223)Ra, or the design of bone-seeking ligands, such as phosphonates, to selectively deliver the radionuclide to the target, e.g. [(153)Sm]Sm-EDTMP. A combination of the above may too be possible, where the bone seeking ligand facilitates the selective accumulation of a radionuclide, which by itself is also bone homing. In terms of therapeutic application radionuclides with various decay modes are proposed, including beta (-) emitters: (153)Sm, (89)Sr, (186)Re, (188)Re, (32)P, (177)Lu and (170)Tm; alpha (α) emitters: (223)Ra and (225)Ra; and Auger or conversion electron emitter: (117)mSn. From a purely diagnostic perspective, the radioisotopes used for imaging include the well known photon emitting (99)mTc, and positron emitters (18)F and (68)Ga. The current status in the development and application of internal radiotherapy for the palliative treatment of bone pain will be discussed, summarizing the progress made and challenges encountered in the process to realizing an effective drug candidate.     

^89SrCl2与^99Tc—MDP联合治疗转移性骨肿瘤疼痛的临床价值

目的：探讨^89SrCl2与云克（^99锝－二甲基二膦酸盐,^99Tc-MDP联合治疗转移性骨肿瘤疼痛的临床价值。方法：68例转移性骨肿瘤患者分别用^89SrCl2单独治疗及与云克联合治疗,观察其疗效。结果：^89SrCl2单独治疗组,止痛总有效率为81．6％转移消失或缩小的总有效率为18．4％,^89SrCl2与云克静脉滴注联合治疗组,止痛总有效率为93．3％,转移灶消失或缩小的总有效率为36．7％。联合治疗组的疗效明显高于单儿治疗组。结论^89SrCl2联合云克对转移性骨肿瘤所致疼痛有明显疗效,且安全无副作用。联合治疗组优于单独治疗组。     

~(153)Sm-EDTMP联合~(99m)Tc亚甲基二膦酸盐治疗多发性骨转移癌的临床观察

目的　评价 1 53钐 -乙二胺四亚甲基膦酸盐 (1 53Sm- EDTMP)与 99m Tc亚甲基二膦酸盐 (商品名云克 )联合应用治疗多发性骨转移癌的疗效。方法　各种骨转移癌 132例 ,随机分组治疗 ,第 1组 4 2例患者仅静脉注射 1 53Sm- EDTMP,1.0× 10 7Bq/ kg,第 2组 5 0例患者 1 53Sm- EDTMP联合 99m Tc亚甲基二膦酸盐治疗 ,1 53Sm- EDTMP用量不变 ,并与静脉注射 1 53Sm- EDTMP后的第 5天开始用 99m Tc亚甲基二膦酸盐连续 5 d。第 3组 4 0例患者静脉滴注博宁 ,10 d1个疗程。结果　第 1组镇痛有效率为 6 1% ,疼痛缓解持续时间平均 4周。第 2组联合用药组镇痛有效率达 80 % ,疼痛缓解持续时间平均 8周。第 3组镇痛有效率 4 2 % ,疼痛缓解持续时间平均 2周。 3组疗效有显著统计学意义 (P<0 .0 5 )。结论　不论 1 53Sm - EDTMP单独使用还是与 99m Tc亚甲基二膦酸盐联合用药都是治疗多发骨转移的有效止痛方法 ,相比之下 ,联合用药可明显提高镇痛效率。     

The role of osteoclastic activity in prostate cancer skeletal metastases

Metastasis of prostate cancer to bone is a common complication of progressive prostate cancer. Skeletal metastases are often associated with severe pain and thus demand therapeutic interventions. Although often characterized as osteoblastic, prostate cancer skeletal metastases usually have an underlying osteoclastic component. Advances in osteoclast biology and pathophysiology have led toward defining putative therapeutic targets to attack tumor-induced osteolysis. Several factors have been found to be important in tumor-induced promotion of osteoclast activity. One key factor is the protein receptor activator of nuclear factor-kappa B ligand (RANKL), which is required to induce osteoclastogenesis. RANKL is produced by prostate cancer bone metastases, enabling these metastases to induce osteolysis through osteoclast activation. Another factor, osteoprotegerin, is a soluble decoy receptor for RANKL and inhibits RANKL-induced osteoclastogenesis. Osteoprotegerin has been shown in murine models to inhibit tumor-induced osteolysis. In addition to RANKL, parathyroid hormone-related protein and interleukin-6 are produced by prostate cancer cells and can promote osteoclastogenesis. Finally, matrix metalloproteinases (MMPs) are secreted by prostate cancer cells and promote osteolysis primarily through degradation of the nonmineralized bone matrix. MMP inhibitors have been shown to diminish tumor establishment in bone in murine models. Thus, many factors derived from prostate cancer metastases can promote osteolysis, and these factors may serve as therapeutic targets. The importance of osteoclasts in the establishment and progression of skeletal metastases has led to clinical evaluation of therapeutic agents to target them for slowing metastatic progression. Bisphosphonates are a class of compounds that decrease osteoclast life span by promoting their apoptosis. The bisphosphonate pamidronate has proven clinical efficacy for relieving bone pain associated with breast cancer metastases and has a promising outlook for prostate cancer metastases. Another bisphosphonate, zoledronic acid, appears to directly target prostate cancer cells in addition to diminishing osteoclast activity at the metastatic site. In addition to bisphosphonates, other novel therapies based on studies that delineate mechanisms of skeletal metastases establishment and progression will be developed in the near future.     

Strategies for management of prostate cancer-related bone pain

Prostate cancer is one of the most common malignancies and a leading cause of cancer-related death in men worldwide. In the majority of cases, prostate cancer metastases to the skeleton, in which case cancer-related bone pain becomes a major cause of morbidity. Androgen ablation is the treatment of choice for securing regression of skeletal metastases in the majority of cases. Intermittent androgen ablation is an attractive alternative, aimed at minimising adverse effects of hormone deprivation but also potentially delaying hormone-refractoriness. The development of hormone-refractoriness is heralded by a significant increase in morbidity largely because of escalating bone pain caused by the progression of the metastatic process. Skillful use of analgesics is initially successful but eventually fails to control symptoms. Localised metastases are best treated with local radiotherapy that is rapidly effective. Over the last few years, it has become clear that therapeutic modalities using bone-seeking radionuclides or bisphosphonates have been effective in the palliation of prostate cancer-related bone pain, although not affecting survival. The main limiting factor with the use of radionuclides is bone marrow suppression, also a feature of the very late stages of prostate cancer. Bisphosphonates do not carry this disadvantage. Results of large double-blind, placebo-controlled studies should be awaited, however, before advocating the widespread use of these agents in the management of patients with prostate cancer and skeletal metastases.