¹⁶⁶Ho-labeled microspheres for radioembolic therapy of hepatocellular carcinoma

Radioembolization with suitable therapeutic isotopes is an effective targeted therapy for hepatocellular carcinoma (HCC), but there is a need for suitable indigenously prepared alternative to imported therapeutic microspheres in this application. ¹⁶⁶Ho can be produced in the reactor and has favorable emission characteristics (T_1/2 = 26.8 h, E_βmax = 1.84 MeV, E = 81 keV) for HCC therapy. It is proposed to γ tag indigenously produced ¹⁶⁶Ho to commercially available resin microspheres and evaluate the radiolabeled product physico-chemically and biologically for its suitability toward the intended application. ¹⁶⁶Ho was produced by (n,γ) irradiation of ¹⁶⁵Ho (as Ho₂O₃) target in Dhruva reactor and processed to give ¹⁶⁶Ho as HoCl₃. Different commercial resin microspheres (BiorexTM 70, BiorexTM 5, Biorex AG® 50W) were tested for ¹⁶⁶Ho-labeling. Optimized formulation of the best-yielding ¹⁶⁶Ho-labeled microsphere was checked for in vitro stability in saline and serum. In vivo distribution and retention of the formulation was tested using our previously reported protocol in Wistar Rat model. ¹⁶⁶Ho was produced with good specific activity (>13G Bq/mg). Using the optimized protocol, BiorexTM 70 was labeled with ¹⁶⁶Ho with >90% yield at pH 8.5. The labeling was stable (>95%) in both saline (pH 7.0) and serum for up to 72h postpreparation. In vivo studies showed >90% retention of ¹⁶⁶Ho activity in the liver at 72 h postinjection with minimal leakage to nonspecific organs. Preparation and preliminary evaluation of ¹⁶⁶Ho- labeled microspheres indicates a potentially viable indigenous alternative to imported radioactive microspheres for treatment of HCC. (author)