Liquid-liquid extraction in flow of the radioisotope titanium-45 for positron emission tomography applications

A continuous liquid-liquid extraction of ^natTi and its PET radioisotope ⁴⁵Ti into an organic phase from 12 M HCl is described. The extraction is completely selective with respect to Sc, which is commonly used as a cyclotron target for ⁴⁵Ti production. A membrane-based separator with integrated pressure control allowed for efficient, reproducible, and robust aqueous/organic phase separation in flow. Optimization studies established a guaiacol-anisole 9/1 (v/v) mixture and a flow rate ratio of 1/3 (aq. to org.), with a residence time of 13.7 s as the optimal extraction conditions. 90.3 ± 1.1% of ^natTi was consistently extracted from a 0.01 M solution of ^natTiCl₄ and ScCl₃, while 84.8 ± 2.4% of ⁴⁵Ti was extracted from 0.03-0.13 M ScCl₃ containing picomolar amounts of the ⁴⁵Ti radionuclide, without extracting any Sc from either system. The organic phase can be directly used for ⁴⁵Ti-radiolabelling as demonstrated by the efficient radiosynthesis of the ⁴⁵Ti-radiolabeled antineoplastic [⁴⁵Ti](salan)Ti(dipic). This development opens a pathway to achieve continuous and efficient ⁴⁵Ti recovery and processing using an automated micro or millifluidics setup.