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

Abstract

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 >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.

Biodistribution and Internal Dosimetry of 68Ga-DOTA-IBA PET Imaging for Patients With Bone Metastases

“…68 Ga-DOTA-IBA was rapidly metabolized in vivo and aggregated in bone metastases after IV injection. This is similar to the previously reported biodistribution of radionuclide-labeled ibandronate ( 177 Lu and 188 Re), 13,19 although where the bifunctional chelate DOTA was not used to bind ibandronate. In the imaging time point used in this study, there was no decreasing trend in SUV of bone metastases, but considering the effect of 68 Ga half-life, it is recommended that the imaging time point should be set at 2 hours.…”

Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

“…Ibandronic (IBA) acid is a third generation bisphosphonate. Studies have reported the labelling of metal ions with IBA acid using complex methods requiring larger amounts of precursors and products that have toxic side effects ( 6 , 7 ). Previous studies have shown that the bifunctional chelate DOTA can be used for the complexation of metal compounds ( 5 ).…”

Recent Development of Rhenium-Based Materials in the Application of Diagnosis and Tumor Therapy

“…In the past decade, the development of 188 Re in nuclear medicine has been slow, with few innovative studies being reported [ 68 , 69 , 70 ]. However, the research on radioactive rhenium has not stopped.…”