Anderson Peter M, Subbiah Vivek, Trucco Matteo M
Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, Cleveland Clinic Children's Hospital, Pediatric Institute, Cleveland Clinic, Cleveland, OH, United States.
Investigational Cancer Therapeutics, Cancer Medicine, Clinical Center for Targeted Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Med (Lausanne). 2022 Nov 15;9:1030094. doi: 10.3389/fmed.2022.1030094. eCollection 2022.
Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 (Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (Ac) or the Her-2 antibody linked to thorium-227 (Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819).
骨肉瘤是一种高级别肉瘤，其特征为类骨质形成、IGF1R几乎普遍表达且有一部分表达HER-2。这些特性为使用发射α粒子的同位素提供了机会，以便除了对表达IFG1R或Her-2的转移灶之外，还能将α粒子精确地靶向骨形成肿瘤进行放射治疗。本综述将详细介绍使用靶向骨形成的α发射体镭-223（Ra，商品名Xofigo）治疗骨肉瘤的经验，具体涉及患者选择、使用吉西他滨进行放射增敏以及使用地诺单抗增加这些癌症的成骨细胞表型。文中描述了一例无法手术的左上叶椎体-椎旁-纵隔成骨细胞病变，经镭联合吉西他滨成功治疗的病例。由于并非骨肉瘤病变的所有区域都是成骨细胞性的，但几乎所有骨肉瘤细胞都过度表达IGF1R，且有一些亚群表达Her-2，与锕-225（Ac）连接的抗IGF1R抗体FPI-1434或与钍-227（Th）连接的Her-2抗体可能成为提供针对骨肉瘤的靶向α粒子治疗的其他手段（NCT03746431和NCT04147819）。
