An optimized formulation for [۹۹mTc]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 [۹۹mTc] Tc to achieve the best formulation in preparing an ideal skeletal radiotracer.  Radio-complex 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 [۹۹mTc]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: [۹۹mTc]Tc-zoledronic acid was prepared easily with high yield while ۱۰۰ µg, ۰.۳۴ µmol of zoledronic acid as a ligand and ۱۰۰ µg, ۰.۴۴ µmol SnCl۲ as a reducing agent were used. Radiochemical purity of radio-complex was more than ۹۹% with specific activity of ۸۰۵۰ MBq/µmol. The radio-complex showed rapid blood washout along with high bone uptake value (۴.۵۳ ± ۰.۱۴ % IA/g at ۲ h post injection).Conclusion: Under optimized condition, [۹۹mTc]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.