Radiopharmaceutical Sciences Program, College of Pharmacy, Health Sciences Center, University of New Mexico, MSC09 5360, Albuquerque, NM, 87131-0001, USA.
Experimental Therapeutics Unit, University of New Mexico Comprehensive Cancer Center, 1210 Camino de Salud, Albuquerque, NM, 87131, USA.
Target Oncol. 2018 Apr;13(2):189-203. doi: 10.1007/s11523-018-0550-9.
Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting. Numerous studies have demonstrated the in vitro and in vivo efficacy of the targeted α-therapy. Radium-223 (Ra) dichloride (Xofigo®) is the first α-emitter to have received FDA approval for the treatment of prostate cancer with metastatic bone lesions. There is a significant increase in the number of clinical trials in oncology using several radionuclides such as Actinium-225 (Ac), Bismuth-213 (Bi), Lead-212 (Pb), Astatine (At) or Radium-223 (Ra) assessing their safety and preliminary activity. This review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.
α-发射体是通过发射高传能线密度的 α 粒子而衰变的放射性核素，具有良好的药理特性，可用于癌症治疗。当与单克隆抗体、肽、小分子或纳米颗粒结合时，α 粒子发射的优异细胞毒性能力引起了人们对探索临床前靶向 α 治疗的强烈兴趣，最近也引起了肿瘤学临床试验的兴趣。研究人员和临床医生克服了多个障碍，加速了靶向 α 疗法的发展，特别是最近同位素生产和纯化的改进，以及优化靶向的创新策略的发展。许多研究已经证明了靶向 α 治疗的体外和体内疗效。镭-223（Ra）二氯化物（Xofigo®）是第一个获得 FDA 批准用于治疗有转移骨病变的前列腺癌的 α 发射器。使用几种放射性核素（如锕-225（Ac）、铋-213（Bi）、铅-212（Pb）、砹（At）或镭-223（Ra））进行的肿瘤学临床试验数量显著增加，评估其安全性和初步疗效。这篇综述将涵盖它们的治疗应用，并总结为进一步临床开发提供基础的研究。
