Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.
镭-223是一种靶向肿瘤诱导成骨细胞的α粒子发射型骨靶向放射性药物，用于减轻骨转移性去势抵抗性前列腺癌患者的骨痛并延长总生存期。然而，在接受镭-223治疗的患者中，观察到无骨转移的骨骼部位骨折风险增加。本研究采用荧光素酶或绿色荧光蛋白标记的成骨细胞报告基因小鼠，监测镭-223对常驻成骨细胞及正常骨结构的影响。通过活体生物发光成像检测发现，镭-223治疗后2天内70%的常驻成骨细胞减少，且这种减少持续至少18周未见明显恢复。在GFP标记的成骨细胞报告基因小鼠中，镭-223主要减少位于骨小梁区域的成骨细胞，而对生长板区域的成骨细胞影响较小。微型计算机断层扫描分析显示，镭-223显著降低股骨骨小梁区域的骨密度和骨微结构，但对皮质骨无显著影响。通过向小鼠股骨接种成骨性TRAMP-BMP4前列腺癌细胞构建肿瘤诱导骨模型，镭-223治疗显著减少了肿瘤诱导的成骨细胞。本研究表明，镭-223会影响未发生骨转移的骨结构。改善骨骼健康的策略可能降低接受镭-223治疗患者的骨折风险。
肿瘤(癌症)患者之家