Automating the production of [Fe18FF2(BnMe2-tacn)] and investigating radiostabilisers for use with high-activity [18F]F−

Abstract

The manual radiofluorination and purification of [FeF3(BnMe2-tacn)] (tacn = 1,4,7-triazacyclononane) using 18F− in aqueous EtOH has been translated to a GE FASTLab™ automatic synthesis platform and optimised by conducting a series of low-activity radiolabelling experiments to explore the effects of varying the precursor concentration, temperature, heating time, addition of NaOAc buffer and EtOH:H2O ratio. The optimal conditions were determined to be 1 mg/mL of the precursor being heated at 120 °C for 10 min in 75 %:25 % EtOH:H2O containing 18F−, with elution using 10 mM NaOAc, giving 61 % radiochemical yield (RCY). These conditions were then employed with high-activity 18F− giving a 97 % radiochemical purity (RCP) at t = 0, which decreases by 22 % over 5 h. Sodium ascorbate, nicotinamide and p-benzoic acid (pABA) were then tested as potential radiostabilisers for this system, initially using low-activity 18F−. These experiments revealed very rapid defluorination of the radioproduct in the presence of sodium ascorbate. In contrast, both nicotinamide and pABA appear to be effective radiostabilisers, resulting in RCP values of 91 % and 89 %, respectively, after 2 h, which compare with an RCP of 81 % under analogous conditions at t = 2 h in their absence. High-activity experiments were then undertaken with addition of 5 mg/mL of nicotinamide, with a radio-active concentration (RAC) of 220 MBq/mL, giving RCY of 26 % and following purification, RCP values for the [Fe18FF2(BnMe2-tacn)] product of 97 % at t = 0 and 86 % after 3 h.