恶性肿瘤的骨转移严重危害患者的生存和生活质量。我们设计和合成了一种新型的双膦酸放射性药物[68Ga-或177Lu-标记的DOTA-Ibandronate(68Ga/177Lu-DOTA-IBA)]，用于骨转移的靶向诊断和治疗。本研究探讨了177Lu-DOTA-IBA的基本生物特性，指导临床翻译，并为未来的临床应用提供了证据。采用控制变量法优化最佳标记条件。研究了177Lu-DOTA-IBA的体外性质、生物分布和毒性。采用微型SPECT/CT对正常小鼠和肿瘤小鼠进行成像。获得伦理委员会批准，招募了五名志愿者进行初步的临床翻译研究。177Lu-DOTA-IBA具有超过98％的放化纯度，具有良好的生物特性和安全性。血液清除速度快，软组织摄取率低。示踪剂主要通过尿系统排泄，在骨中靶向和持续浓缩。三名患者在177Lu-DOTA-IBA治疗(740-1110 MBq)后3天内感受到明显的疼痛缓解，持续时间超过2个月，无毒副作用。177Lu-DOTA-IBA易于制备且具有良好的药代动力学特性。低剂量177Lu-DOTA-IBA是有效的，耐受性良好，未出现明显的不良反应。它是一种有前途的放射性药物，可用于骨转移的靶向治疗，控制骨转移的进展，改善晚期骨转移患者的生存和生活质量。

Bone metastases of malignant tumors significantly threaten the patient survival and quality of life. We designed and synthesized a novel bisphosphonate radiopharmaceutical [68Ga- or 177Lu-labeled DOTA-Ibandronate(68Ga/177Lu-DOTA-IBA)] for targeted diagnosis and treatment of bone metastases. This study explored the basic biological characteristics of 177Lu-DOTA-IBA, guiding clinical translation and providing evidence for future clinical applications. The control variable method was used to optimize the optimal labeling conditions. The in vitro properties, biological distribution, and toxicity of 177Lu-DOTA-IBA were studied. Normal mice and tumor-bearing mice were imaged using micro SPECT/CT. With Ethics Committee approval, five volunteers were recruited for a preliminary clinical translation study. 177Lu-DOTA-IBA has a radiochemical purity of more than 98%, with good biological properties and safety. Blood clearance is fast and soft tissue uptake is low. Tracers are excreted mainly through the urinary system, targeting and continuously concentrating in the bones. Three patients experienced significant pain relief within 3 days after 177Lu-DOTA-IBA treatment (740-1110 MBq), lasting more than 2 months, with no toxic side effects. 177Lu-DOTA-IBA is easy to prepare and exhibits good pharmacokinetic characteristics. Low-dose 177Lu-DOTA-IBA is effective, well tolerated, and was associated with no significant adverse reactions. It is a promising radiopharmaceutical for the targeted treatment of bone metastases, controlling the progress of bone metastasis and improving survival and quality of life of patients with advanced bone metastasis.