Duke Cancer Institute, Durham, NC, USA.
Cancer Manag Res. 2013;5:1-14. doi: 10.2147/CMAR.S25537. Epub 2013 Jan 8.
Radium-223 chloride ((223)Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), (223)Ra delivers a high quantity of energy per track length with short tissue penetration.
This review describes the mechanism, radiobiology, and preclinical development of (223)Ra and discusses the clinical data currently available regarding its safety and efficacy profile.
Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.
Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, (223)Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, (223)Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents.
镭-223 氯化物（(223)Ra；阿尔法放射素）是一种靶向成骨性转移部位的α 发射放射性同位素，可通过小肠排出体外。与β 发射体（例如锶-89、钐-153）相比，(223)Ra 每单位长度的轨迹传递更多能量，且组织穿透深度较短。
本综述描述了(223)Ra 的作用机制、放射生物学和临床前开发，并讨论了目前关于其安全性和疗效特征的临床数据。
通过使用 PubMed 数据库和美国临床肿瘤学会摘要数据库，收集并分析了临床试验数据（包括摘要）。
目前的骨靶向治疗方法分为两类：抗吸收剂（例如唑来膦酸、地诺单抗），它们已被证明可延迟骨骼相关事件；放射性药物（例如钐-153），可能在缓解疼痛方面有一定作用。从历史上看，抗吸收剂和放射性药物都没有明确证据表明在转移性去势抵抗性前列腺癌（mCRPC）中改善总体生存率或其他抗肿瘤作用。放射性药物受到骨髓抑制、血小板减少和肾排泄的限制。在最近报告的一项针对接受或不能接受多西他赛化疗的有症状骨转移 CRPC 男性的随机 III 期试验中，(223)Ra 治疗可改善总体生存率并延迟骨骼相关事件。毒性包括轻微的胃肠道副作用以及轻度中性粒细胞减少和血小板减少，很少严重。在等待监管部门批准的情况下，(223)Ra 可能成为 mCRPC 重要亚组患者的独特而独特的选择；未来的试验应解决其与现有和新型药物联合或序贯使用的问题。
