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 [ 68 Ga- or 177 Lu-labeled DOTA-Ibandronate( 68 Ga/ 177 Lu-DOTA-IBA)] for targeted diagnosis and treatment of bone metastases. This study explored the basic biological characteristics of 177 Lu-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 177 Lu-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. 177 Lu-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 177 Lu-DOTA-IBA treatment (740-1110 MBq), lasting more than 2 months, with no toxic side effects. 177 Lu-DOTA-IBA is easy to prepare and exhibits good pharmacokinetic characteristics. Low-dose 177 Lu-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.