166Dy/166Ho-labeled porous hydroxyapatite microparticles for treatment of inflammatory joint diseases – Exploring the advantages of in vivo generator

Holmium-166 [T_½ = 26.8 h, E_β^- (max) = 1.74 MeV (48.7%) and 1.85 MeV (50.0%); Eγ = 80.6 keV (10.6%)] is one of the most promising radionuclides in radiation synovectomy (RSV) for the treatment of inflammatory joint diseases, especially of large joints. However, short half-life of ¹⁶⁶Ho is a practical impediment toward its extensive utility. This study aims to address this limitation by developing a potent formulation where ¹⁶⁶Ho in transient radioactive equilibrium with ¹⁶⁶Dy [T_½ = 81.5 h] is used as its in vivo generator. In this regard, a chelator-free radiolabeling approach was optimized using porous hydroxyapatite (HA) microsphere (2-10 μm) as a carrier platform of ¹⁶⁶Dy/¹⁶⁶Ho. Sorption of ¹⁶⁶Dy/¹⁶⁶Ho in porous HA followed Langmuir-Freundlich isotherm and pseudo-second order kinetics, indicating chemisorption of the radiolabeling process. The formulation retained its radiochemical integrity in PBS and human serum upto a period of 14 d. The preclinical study showed near-exclusive retention of the radiolabeled microparticles within the injected joint cavity of healthy Wistar rats with no translocation of ¹⁶⁶Dy and ¹⁶⁶Ho. Overall, the reported studies indicated the potency developed ¹⁶⁶Dy/¹⁶⁶Ho-labeled porous HA microsphere for the treatment of inflammatory joint diseases and an in vivo generator of ¹⁶⁶Ho.