Production of no-carrier-added Ho-166 for targeted therapy purposes

Introduction: Holmium-166 radionuclide is one of the most effective radionuclides used for targeted therapy with theranostic properties. One method to produce this radioisotope is via the decay of its parent (indirect method). In this study applicability of extraction chromatography (EXC) for separation of no carrier added 166Ho from neutron-irradiated natural dysprosium target followed by quality control procedures have been demonstrated. Methods: 166Dy was produced by thermal neutron bombardment (5×1013n/cm2.s) of natural 164Dy target through 164Dy (n,γ) 165Dy (n,γ) 166Dy process in a nuclear reactor. The generator-produced 166Ho was separated from 166Dy by extraction chromatographic method. The extractant used in resin was 2-ethylhexyl 2-ethylhexylphosphonic acid (HEH[EHP]). The final solution went through radionuclide, chemical and radiochemical purity tests. Results: Using 1.5 M HNO3 as eluent at 25 °C, and flow rate of 1.5 mL/min, quantitative separation between Ho and Dy was achieved using LN2 resin in 1.5 h to yield in no carrier added 166HoCl3 (radionuclide purity >99.9%; separation yield; 76% and radiochemical purity >99% ITLC). Conclusion: High specific activity 166HoCl3 produced in this study is highly suitable for metal sensitive labeling of monoclonal antibodies, fragments and especially peptides to yield efficient therapeutic doses for human applications.