Preparation, quality control and biodistribution assessment of ¹⁵³Sm-BPAMD as a novel agent for bone pain palliation therapy

Abstract

Objective

Various phosphonate ligands labeled with β⁻-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed.

Methods

¹⁵³Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (¹⁵³Sm-BPAMD) complex was prepared using BPAMD ligand and ¹⁵³SmCl₃. The effect of various parameters on the labeling yield of ¹⁵³Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post-injection. The biodistribution of the complex was compared with the biodistribution of the ¹⁵³Sm cation in the same type mice.

Results

¹⁵³Sm-BPAMD was prepared in high radiochemical purity >98 % and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP _o/w was −1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue.

Conclusion

The results show that ¹⁵³Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed.