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Background. Bone is a common site of metastasis from a malignant tumor. Several radiopharmaceuticals are available to relieve bone pain in patients with cancer. However, every radiopharmaceutical has its own disadvantages, and there is still a need to investigate easily accessible and high bone affinity radiopharmaceuticals. Ibandronate (IBA) and 188Re were used for radiolabeling to develop and evaluate a novel type of bone-seeking radiopharmaceutical. Methods. The preparation conditions of [188Re]Re-IBA were investigated, and thin-layer chromatography was used to analyze radiochemical purity. The stability, plasma protein binding rate, lipid-water distribution coefficient, safety and biodistribution in normal mice, and bone imaging of [188Re]Re-IBA in New Zealand rabbits were studied. In addition, the nude mice model of bone metastasis was established, and biodistribution and imaging characteristics of [188Re]Re-IBA in these nude mice were studied. Results. [188Re]Re-IBA was successfully prepared with radiochemical purity &gt;95%. The optimum preparation conditions were as follows: IBA, 0.8–1.4 mg; ascorbic acid, 0.2–0.5 mg; stannous chloride, 0.14–0.18 mg; potassium perrhenate, 0.005 mg; and [188Re]ReO4- activity, 18.5–296 MBq, reacted for 30 min at 95°C with pH = 2. [188Re]Re-IBA demonstrated good stability, high plasma protein binding rate, good hydrophilicity, and low toxicity. The biodistribution and bone imaging in normal animals showed rapid blood clearance, high bone uptake, low uptake in the solid organs and soft tissue, and high contrast during imaging. The biodistribution and imaging of bone metastasis in nude mice showed that [188Re]Re-IBA has higher uptake in bone metastasis lesions than normal bone. Conclusions. Our study encompassed the successful preparation of [188Re]Re-IBA, a novel bone-seeking radiopharmaceutical, and confirmed it has potential in the treatment of bone metastasis and monitoring through imaging.

Preparation, Characterization, and Preliminary Imaging Study of [188Re]Re-Ibandronate as a Novel Theranostic Radiopharmaceutical for Bone Metastasis