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.