Highly efficient production of [¹⁸F]fallypride with low concentration of base

Objectives [¹⁸F]Fallypride exhibits an effective radiotracer for the study of dopamine D₂/D₃ receptor occupancy, neuropsychiatric disorders and aging in humans. However, automated labeling efficiency showed moderate radiochemical yields about 5-40% with relatively long incorporation time of fluorine-18, preceded high temperatures (150-165 °C) or involved the use of an unusual microwave system in automatic devices. In present study, we describe an automated radiochemical synthesis of [¹⁸F]fallypride in different base concentration and incorporation time of fluorine-18 for potentially utilizable in routine production sites.

Methods To minimization of base concentration of phase-transfer catalyst, [¹⁸F]fluoride was extracted with different concentrations of tetrabutylammonium bicarbonate (TBAHCO₃) or Kryptofix 2.2.2./K₂CO₃ in organic solvent such as CH₃CN/H₂O or MeOH/H₂O from ¹⁸O-enriched water trapped on the activated ion exchange cartridge (Chromafix® PS-HCO3). After azeotropic drying, the labeling reaction proceeded in CH₃CN at 100 °C for 10 or 30 min. The desired product, [¹⁸F]fallypride, was purified by reverse phase HPLC and collected solution was exchanged for 10% ethanol in saline using tC18 Sep-Pak for clinical research.

Results The radiochemical yield was increased according to decreasing amounts of base concentration. The labeling condition of [¹⁸F]fallypride was optimized that 2 mg of tosyl-fallypride in acetonitrile (1 mL) was heated at 100 °C for 10 min with 40% TBAHCO₃ (10 μL). [¹⁸F]Fallypride was obtained with high radiochemical yield about 68 ± 1.6% (decay-corrected, n = 8) within 51 ± 1.2 min including HPLC purification and solid-phase purification. The specific activity showed about 140-192 GBq/μmol.

Conclusions [¹⁸F]Fallypride was prepared with a significantly improved radiochemical yield with high specific activity and shorten synthetic time. This automated procedure for [¹⁸F]fallypride production could facilitate its routine clinical use in dopamine D₂/D₃ studies