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

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Abstract
44 Ti/ 44 Sc radionuclide generators are of interest for molecular imaging. The 3.97 h half-life of 44 Sc and its high positron branching of 94% may stimulate the application of 44 Sc labelled PET radiopharmaceuticals. However, both 44 Ti production and 44 Ti/ 44 Sc generator design represent challenges for basic radiochemistry. About 5 mCi (185 MBq) of 44 Ti were obtained via the Sc( p , 2 n ) nuclear reaction. 44 Ti 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 44 Ti/ 44 Sc generator concept, distribution coefficients of Ti(IV) and Sc(III) on both AG 1-X8 (200−400 mesh, Cl - -form) and AG 50W-X8 (200−400 mesh, H + -form) resins eluted with HCl and HCl/H 2 C 2 O 4 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 0.07 M HCl and 0.005 M H 2 C 2 O 4 . 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 44 Sc in 20 mL of eluate solution. The breakthrough of 44 Ti is 90 Bq. This corresponds to an excellent separation factor of 2×10 6 . In the context of long-term stability of 44 Ti/ 44 Sc generators, a “reverse” type of washing steps after each elution using 0.07 M HCl/0.005 M H 2 C 2 O 4 mixtures appeared to be essential.

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