3.4. Radiochemistry

The aqueous solution of no-carrier-added [¹⁸F]fluoride (1–2 GBq) was trapped on a Chromafix^® 30 PS-HCO₃⁻ cartridge (MACHEREY-NAGEL GmbH & Co. KG, Düren, Germany). The activity was eluted with 300 µL of an aqueous K₂CO₃-solution (1.78 mg, 12.9 µmol) into a 4 mL V-vial containing Kryptofix 2.2.2 (K₂₂₂, 11.2 mg, 29.7 µmol) in 1 mL MeCN. The K⁺/[¹⁸F]F⁻/K₂₂₂-carbonate complex was azeotropically dried under vacuum and nitrogen flow within 7–10 min using a Discover PETwave Microwave CEM^® (75 W, 50–60 °C, power cycling mode). Two aliquots of MeCN (2 × 1.0 mL) were added during the drying procedure and the final complex was dissolved in 500 µL MeCN ready for radiolabelling.

The aliphatic radiolabelling of the tosylate TA5a (1 mg in 500 µL MeCN) was performed under conventional heating at 80 °C for 15 min. Aliquots of the reaction mixture were analyzed by radio-TLC (EtOAc/DCM, 1:1, v/v) to determine the radiochemical yield of the crude product. After dilution with water (1:1, v/v), the crude reaction mixture was applied to an isocratic semi-preparative HPLC (see General Information) for isolation of the desired radioligand [¹⁸F]TA5 (t_R = 34–38 min). The collected fractions were diluted with water (total volume: 40 mL), passed through a Sep-Pak^® C18 Plus light cartridge (Waters, Milford, MA, USA; pre-conditioned with 20 mL of absolute EtOH and 60 mL water), and eluted with 0.75 mL of absolute EtOH. Evaporation of the solvent at 70 °C under a gentle nitrogen stream and subsequent formulation of the radioligand in sterile isotonic saline containing 10% EtOH (v/v) afforded a [¹⁸F]TA5-solution usable for biological investigations.

The identity of the radioligand was proved by analytical radio-HPLC (see General Information) of samples of [¹⁸F]TA5 spiked with the non-radioactive reference compound TA5 using a gradient and an isocratic mode.