(166)Dy/(166)Ho-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 (166)Ho is a practical impediment toward its extensive utility. This study aims to address this limitation by developing a potent formulation where (166)Ho in transient radioactive equilibrium with (166)Dy [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 (166)Dy/(166)Ho. Sorption of (166)Dy/(166)Ho 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 (166)Dy and (166)Ho. Overall, the reported studies indicated the potency developed (166)Dy/(166)Ho-labeled porous HA microsphere for the treatment of inflammatory joint diseases and an in vivo generator of (166)Ho.