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

Abstract

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.