Production, quality control, biodistribution assessment and preliminary dose evaluation of ¹⁶⁶Ho-alendronate as a bone marrow ablative agent

Abstract

In this study, production, quality control and biodistribution studies of ¹⁶⁶Ho-alendronate have been presented and followed by dosimetric evaluation for human based on biodistribution data in wild-type rats. ¹⁶⁶Ho chloride was obtained by thermal neutron irradiation of natural ¹⁶⁵Ho(NO₃)₃ samples. ¹⁶⁶Ho-alendronate complex was prepared by adding the desired amount of alkaline alendronate solution (0.2 mL, 150 mg/mL) to 3–5 mCi of the ¹⁶⁶HoCl₃ solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). ¹⁶⁶Ho-alendronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The major accumulation of the radio-complex was in the bone tissues followed by absorbed dose evaluation of each human organ by RADAR software used for modelling the radiation dose delivered. The final preparation was administered to wild-type rats and biodistribution of the complex was performed 2–48 h post injection showing major accumulation of the complex in the bone tissue. The highest absorbed dose for ¹⁶⁶Ho-alendronate is observed in bone surface and red marrow with 2.670 and 1.880 mSv/MBq; respectively. These findings suggest that ¹⁶⁶Ho-alendronate has considerable characteristics compared to ¹⁶⁶Ho-DOTMP and can be a possible candidate for bone marrow ablation in patients with multiple myeloma.