Development of a SnO₂-based ⁴⁴Ti/⁴⁴Sc generator for medical applications

Towards application of ⁴⁴Sc for diagnostic nuclear medicine, a ⁴⁴Ti/⁴⁴Sc generator based on an inorganic resin has been evaluated. Unlike other radionuclide generators used for medical applications, the long-term retention of the parent ⁴⁴Ti is vital due to its long half life. Herein, tin dioxide (SnO₂), a robust inorganic-based resin, has been synthesized and used as the stationary phase for a ⁴⁴Ti/⁴⁴Sc generator. The sorption behavior of ⁴⁴Ti/⁴⁴Sc was tested on SnO₂ with varying acids, concentrations, and times. Preliminary batch study results showed >88 % ⁴⁴Ti retention to the resin at lower acid concentrations (0.05 M HNO₃ and 0.05 M HCl). A pilot generator was evaluated for a year, demonstrating 85.3 ± 2.8 % ⁴⁴Sc elution yields and 0.71 ± 0.14 % ⁴⁴Ti breakthrough in 5 M HNO₃. Based on capacity studies, a 7.4 MBq (200 µCi) upscaled generator system was constructed for further evaluation of the SnO₂ resin stability and the efficacy of the eluted ⁴⁴Sc for radiolabeling. ⁴⁴Sc could be regularly eluted from this generator in 5 M HNO₃ with an overall average radiochemical yield 84.7 ± 9.5 %. Post-elution processing of the ⁴⁴Sc with DGA-normal resin removed all ⁴⁴Ti present and allowed for high ⁴⁴Sc-DOTA labeling yields of 94.2 ± 0.5 %. Overall, SnO₂ has been shown to be a viable material for a ⁴⁴Ti/⁴⁴Sc generator.