Lutetium177-Labeled DOTA-Ibandronate: A Novel Radiopharmaceutical for Targeted Treatment of Bone Metastases

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.