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Polymeric Microspheres for Radionuclide Synovectomy Containing Neutron-Activated Holmium-166

Division of Medicinal Chemistry and Pharmaceutics, Center of Membrane Sciences, and Division of Nuclear Medicine, University of Kentucky, Lexington, Kentucky

Correspondence: For reprints contact: Michael Jay, PhD, Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082.

ABSTRACT

Poly-L-lactic acid (PLA) microspheres containing neutron-activated ¹⁶⁵Ho were investigated as potential agents for radionuclide synovectomy. Stable ¹⁶⁵Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 µm (range 2–13 µm) containing 25.4% ¹⁶⁵Ho-AcAc (9.1% ¹⁶⁵Ho) were irradiated in a high neutron flux to produce 31.1–36.0 mCi ¹⁶⁵Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 ± 0.01% of the ¹⁶⁶Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257–591 µCi ¹⁶⁶Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed ¹⁶⁶Ho retention in the joint space after 120 hr of 97.7% ± 0.8% and 98.2% ± 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the ¹⁶⁶Ho make them attractive agents for radionuclide synovectomy.