An optimized formulation for [99mTc]Tc radiolabeling of zoledronic acid as bone imaging agent.

Introduction: The aim of this study was to develop an optimized formulation for labeling a third-generation bisphosphonate, zoledronic acid with [99mTc] Tc to achieve the best formulation in preparing an ideal skeletal radiotracer. Radiocomplex yield and purity, stability, biodistribution and imaging in normal rat were investigated. Methods: The samples containing different amounts of zoledronic acid, ascorbic acid and stannous chloride were prepared and labeled with [99mTc]technetium pertechnetate. TLC methods were used to determine the radiochemical purity. The stability was determined in saline and human serum solutions. Lipophilicity was calculated by measuring radio-complex that was divided between organic and aqueous phases. In vitro bone affinity was studied through hydroxyapatite binding assays. Considering the decomposition of radioactivity, biodistribution of radio-complex was assessed based on the percentage of injected activity per gram of organ (% IA/g). Results: [99mTc]Tc-zoledronic acid was prepared easily with high yield while 100 µg, 0.34 µmol of zoledronic acid as a ligand and 100 µg, 0.44 µmol SnCl2 as a reducing agent were used. Radiochemical purity of radio-complex was more than 99% with specific activity of 8050 MBq/µmol. The radio-complex showed rapid blood washout along with high bone uptake value (4.53 ± 0.14 % IA/g at 2 h post injection). Conclusion: Under optimized condition, [99mTc]Tc-zoledronic acid was prepared with high purity and stability together with high bone affinity and rapid blood clearance, make this radio-complex an ideal agent with great potential for skeletal imaging. [ABSTRACT FROM AUTHOR]