Synthesis and Biological Evaluation of Holmium-166 Agglomerated Iron Oxide Nanoparticles for Treatment of Arthritis of Knee Joints

Objectives Owing to its ideally suited nuclear decay properties [T½ = 26.9 h, Eβ( max) = 1.85 MeV, E(gamma) = 81 keV (6.4%)] and availablity in adequate quantity at an affordable cost, 166Ho is an attractive choice for treatment of arthritis of knee joints. Synthesis, characterization and biological evaluation a novel 166Ho-labeled formulation for radiation synovectomy of knee joints using highly agglomerated iron oxide nanoparticles (IONP) having 1-10 μm size range are reported.

Methods Holmium-166 was produced by thermal neutron bombardment on natural Ho2O3 target in a research reactor. Agglomerated iron oxide nanoparticles were synthesized by chemical route and characterized by XRD, FT-IR, SEM, EDX and TEM analysis. Radiolabeling of the agglomerated nanoparticles with 166Ho was achieved by mixing ~185 MBq of 166HoCl3 solution with a suspension of r mg of particles in 0.1 M NaHCO3 solution at pH ~8 and constant stirring the mixture at room temperature for 30 min. Unlabeled 166Ho+3 was separated from the reaction mixture by carefully removing the supernatant solution after precipitation of radiolabeled particles achieved applying magnetic field. In vitro stability of the purified 166Ho-labeled particles was studied in normal saline and rat serum at 37 °C. Biological evaluation of 166Ho-labeled IONP was studied by carrying out biodistribution and radio-luminescence imaging in normal Wistar rats after intra-artcular injection of the labeled particles into one the knee joints of the animals.

Results The synthetic protocol followed led to the formation of agglomerated IONPs having particle size distribution in the range of 1-10 μm, suitable for use as carrier particulates for radiation synovectomy applications. Under optimized conditions, the particles could be radiolabeled with 166Ho with high yield and excellent radiochemical purity of 99.1 ± 0.2%. In vitro studies demonstrated that 166Ho-labeled IONP have excellent stability up to ~4 half-lives of 166Ho when stored in normal saline as well as rat serum at 37°C. In vivo studies in animal model confirmed the localized administration of 166Ho-loaded particles into one of the knee joint cavities with retention of > 98% of the injected activity upto 72 h post-administration.

Conclusions The developed radiochemical formulation could emerge as a potential potential radiopharmaceutical for treatment of arthritis of knee joints.

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