A study on the preparation, evaluation of biological characteristics, and preliminary imaging of [188Re]Re-ibandronate

Abstract

Background Bone is a common site of metastasis of malignant tumor. Several radiopharmaceuticals are available to relieve bone pain in patients with cancer. However, there is still a need to to investigate easily accessible and high bone affinity radiopharmaceuticals. Radionuclide 188Re has an advantage in this regard because of its commercial extraction from 188W/188Re generators. It can be used on demand and is cost-effective. The first-generation bisphosphonate hydroxyethylidene diphosphonate (HEDP) is the commonly used bisphosphonate for 188Re-labelling. And the third-generation bisphosphonates ibandronate (IBA) has higher bone affinity and ability to inhibit bone resorption than HEDP. However, there have been no reports on 188Re-labelling with IBA. We used IBA and 188Re for radiolabeling to develop and evaluate a novel type of bone-seeking radiopharmaceutical. Results We successfully prepared [188Re]Re-IBA in > 95% RCP. The optimum preparation conditions were as follows: IBA, 1.2–1.6 mg; ascorbic acid, 0.20–0.35 mg; stannous chloride, 0.14–0.18 mg; potassium perrhenate, 0.005–0.009 mg; and [188Re]ReO4− activity, 18.5–55 MBq, were reacted for 30 min at 95℃ and pH = 2. [188Re]Re-IBA demonstrated good stability in vitro, high plasma protein binding rate, and good hydrophilicity. The in vivo distribution of mice and bone imaging in New Zealand rabbits showed high bone uptake, long retention time, rapid blood clearance, and relatively low soft tissue uptake. Conclusion Our study encompassed the successful preparation of [188Re]Re-IBA, a novel bone-seeking radiopharmaceutical, and confirmed it has great potential for the treatment of bone pain and imaging monitoring.