Development of a two-vial kit for formulation of therapeutically relevant dose of ¹⁶⁶Ho- chitosan complex

The use of radioembolization agents based on radiolabeled viscous liquid holds tremendous promise in liver cancer therapy. Among such agents, ¹⁶⁶Ho- chitosan complex is particularly attractive because of the excellent nuclear decay characteristics of ¹⁶⁶Ho (T_1/2)= 26.8 h, high energy β- emission with E_max of 1.74 MeV (48.7%) and 1.85 MeV (50.0%) and low energy (80.6 keV) γ-photon emission and large-scale production feasibility of the radioisotope via simple ¹⁶⁵Ho (n,γ) ¹⁶⁶Ho reaction with adequate specific activity in medium flux research reactors. Biodegradability and biocompatibility of chitosan are the other desirable attributes favouring its clinical use. For convenient formulation of therapeutically relevant dose of this radiopharmaceutical in a hospital radiopharmacy, a facile kit based approach has been developed. The kit comprised of two sterile vials. In the first vial (vial A), 4 mL of sterile 1 % acetic acid solution was taken and in the second vial (vial B) 40 mg of chitosan and 20 mg of ascorbic acid were taken. Subsequently, the vials were sealed and autoclaved for 20 min at 120 °C. For formulation of ¹⁶⁶Ho- chotosan complex, ∼7.4 GBq of ¹⁶⁶HoCl₃ solution was added to vial A and mixed well. The content of this vial was withdrawn using a sterile syringe and transferred to vial B. The reaction mixture in vial B was vortexed for 1 min and it was then allowed to stand for 15 min at room temperature. Therapeutically relevant doses (~ 7.4 GBq) of ¹⁶⁶Ho- chitosan complex prepared using the kit, which exhibited satisfactory in vitro stability in phosphate buffered saline (PBS) as well as in human serum at 37° C up to 24 h post-formulation period studied. Biodistribution studies in normal Wistar rats showed excellent retention of the radiopharmaceutical in the liver. The promising results obtained in this study would pave the way towards widespread utility of this approach in clinical context. (author)