[⁹⁰Y]Yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to "TheraSphere" for Cost-Effective Treatment of Liver Cancer

Background: Selective internal radiation therapy (SIRT) using a suitable beta-emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 [T-1/2 = 64.2 h, E-beta(max) = 2.28 MeV, no detectable gamma-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics.Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [Y-90]yttria alumino silicate ([Y-90]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients.Methods: YAS glass microspheres of composition 40Y(2)O(3)-20Al(2)O(3)-40SiO(2) (w/w) and diameter ranging between 20 and 36 mu m were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [Y-90]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [Y-90]YAS glass microspheres were administered in human patients.Results: [Y-90]YAS glass microspheres were produced with 137.7 +/- 8.6 MBq/mg YAS glass (similar to 6800 Bq per microsphere) specific activity and 99.94% +/- 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [Y-90]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe.Conclusions: The study confirmed the suitability of indigenously prepared [Y-90]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.