双膦酸盐通过抑制骨吸收来控制骨肿瘤。本研究探讨了 [177Lu]Lu-P15-073（一种新型双膦酸盐）用于骨转移放射配体治疗 (RLT) 的治疗潜力。 10 名确诊骨转移的患者（年龄 35 至 75 岁）接受了单剂量 [177Lu]Lu-P15-073 的治疗。 177Lu]Lu-P15-073（1,225 ± 84 MBq，或 33 ± 2 mCi）。治疗前，通过[99mTc]Tc-MDP骨扫描验证骨转移。连续平面全身扫描监测 14 天的生物分布。对主要器官和肿瘤病变的剂量测定进行评估，同时通过血液生物标志物和疼痛评分评估安全性。连续平面全身扫描显示[177Lu]Lu-P15-073在骨转移中快速大量积累，而血液中的摄取量极少和其他器官。关键器官红骨髓的吸收剂量测量为（0.034±0.010 mSv/MBq），与其他 177Lu 标记的双膦酸盐相比，标准化有效剂量明显较低（0.013±0.005 mSv/MBq）。观察到骨转移持续高摄取，导致肿瘤剂量升高（中位 3.12 Gy/GBq）。患者对[177Lu]Lu-P15-073疗法表现出良好的耐受性，没有出现新的副作用。此外，87.5% (7/8) 的患者疼痛量表显着降低（数字评定量表，NRS，从 5.1±2.3 降至 3.0±1.8）。 [99mTc]Tc-MDP 的肿瘤背景比 (TBRmean) 与 [177Lu]Lu-P15-073 摄取显着相关 (P < 0.01)，表明其预测吸收剂量的潜力。本研究证明了其安全性、剂量测定、以及[177Lu]Lu-P15-073单次治疗剂量对骨转移的疗效。该治疗耐受性良好，未出现严重不良事件。这些发现表明，[177Lu]Lu-P15-073 有希望成为一种新型 RLT 药物，用于治疗骨转移。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [177Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases.Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [177Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [99mTc]Tc-MDP bone scans. Serial planar whole-body scans monitored biodistribution over a 14-day period. Dosimetry was assessed for major organs and tumor lesions, while safety was evaluated through blood biomarkers and pain scores.Serial planar whole-body scans demonstrated rapid and substantial accumulation of [177Lu]Lu-P15-073 in bone metastases, with minimal uptake in blood and other organs. The absorbed dose in the critical organ, red marrow, was measured at (0.034 ± 0.010 mSv/MBq), with a notably low normalized effective dose (0.013 ± 0.005 mSv/MBq) compared to other 177Lu-labeled bisphosphonates. Persistent high uptake in bone metastases was observed, resulting in elevated tumor doses (median 3.12 Gy/GBq). Patients exhibited favorable tolerance to [177Lu]Lu-P15-073 therapy, with no new instances of side effects. Additionally, 87.5% (7/8) of patients experienced a significant reduction in pain scale (numerical rating scale, NRS, from 5.1 ± 2.3 to 3.0 ± 1.8). The tumor-background ratio (TBRmean) of [99mTc]Tc-MDP correlated significantly with [177Lu]Lu-P15-073 uptake (P < 0.01), indicating its potential for prediction of absorbed dose.This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [177Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [177Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.