A Ti-44/Sc-44 radionuclide generator for potential application of Sc-44-based PET-radiopharmaceuticals

Ti-44/Sc-44 radionuclide generators are of interest for molecular imaging. The 3.97 h half-life of Sc-44 and its high positron branching of 94% may stimulate the application of Sc-44 labelled PET radiopharmaceuticals. However, both Ti-44 production and generator design represent challenges for basic radiochemistry. About 5 mCi (185 MBq) of Ti-44 were obtained via the Se(p, 2n) nuclear reaction. 44Ti was separated from 1.5 g of massive scandium targets in multi-step procedures, including exchange chromatography on cation exchange resin (AG 50W-X8, 200-400 mesh, H+-form). In order to design a robust Ti-44/Sc-44 generator concept, distribution coefficients of Ti(IV) and Sc(III) on both AG 1-X8 (200-400 mesh, CI--form) and AG 50W-X8 (200-400 mesh, H+-form) resins eluted with HCl and HCl/H2C2O4 solution of various concentrations were investigated systematically. Optimal conditions for efficient separations of both radionuclides have been determined for AG 1-X8 resin and mixtures of 0.07M HCl and 0.005M H2C2O4. A 5 mCi generator was prepared on an AG 1-X8 column (H = 150 mm, D = 3 mm, V-0 = 0.55 mL). The system achieved elution of 180 MBq Sc-44 in 20 mL of eluate solution. The breakthrough of Ti-44 is 90 Bq. This corresponds to an excellent separation factor of 2 x 10(6). In the context of long-term stability of Ti-44/Sc-44 generators, a reverse type of washing steps after each elution using 0.07 M HCl/0.005 M H2C2O4 mixtures appeared to be essential.