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

Holmium-166 [T = 26.8 h, E (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 Ho is a practical impediment toward its extensive utility. This study aims to address this limitation by developing a potent formulation where Ho in transient radioactive equilibrium with Dy [T = 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 Dy/Ho. Sorption of Dy/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 Dy and Ho. Overall, the reported studies indicated the potency developed Dy/Ho-labeled porous HA microsphere for the treatment of inflammatory joint diseases and an in vivo generator of Ho.