Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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[177Lu]Lu-P15-073 剂量学、安全性和有效性的首次人体研究：一种用于治疗骨转移的新型基于双膦酸盐的放射配体治疗 （RLT） 药物

 目的

双膦酸盐通过抑制骨吸收在治疗骨肿瘤中起关键作用。本研究调查了 [¹⁷⁷Lu]Lu-P15-073（一种新型双膦酸盐）在骨转移中放射配体治疗 （RLT） 的治疗潜力。

 方法

10 例确诊骨转移的患者 （年龄 35 至 75 岁） 接受了单剂量 [¹⁷⁷Lu]Lu-P15-073 （1,225 ± 84 MBq，或 33 ± 2 mCi） 的治疗。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了 14 天内的生物分布。对主要器官和肿瘤病变进行剂量测定评估，同时通过血液生物标志物和疼痛评分评估安全性。

 结果

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，在血液和其他器官中的摄取最少。关键器官红骨髓的吸收剂量为 （0.034 ± 0.010 mSv/MBq），与其他 ^{177 种 Lu}标记的双膦酸盐相比，标准化有效剂量 （0.013 ± 0.005 mSv/MBq） 明显较低。观察到骨转移的持续高摄取，导致肿瘤剂量升高 （中位数 3.12 Gy/GBq）。患者对 [¹⁷⁷Lu]Lu-P15-073 治疗表现出良好的耐受性，没有新的副作用实例。此外，87.5% （7/8） 的患者疼痛量表 （数字评定量表，NRS，从 5.1 ± 2.3 降至 3.0 ± 1.8） 显著降低。[^99mTc]Tc-MDP 的肿瘤背景比 （TBRmean） 与 [¹⁷⁷Lu]Lu-P15-073 摄取显著相关 （P < 0.01），表明其预测吸收剂量的潜力。

 结论

本研究证明了单一治疗剂量 [¹⁷⁷Lu]Lu-P15-073 在骨转移中的安全性、剂量学和有效性。治疗耐受性良好，无严重不良事件。这些发现表明 [¹⁷⁷Lu]Lu-P15-073 有望成为骨转移的新型 RLT 药物。