The synthesis conditions of [18F]fallypride (Figure 3A ) were adapted and further optimized from our previous work synthesizing this compound using EWOD chips 13 .
A [18F]fluoride stock solution was prepared by mixing [18F]fluoride/[18O]H2O (100 μL, ~370 MBq; ~10 mCi) with 75 mM TBAHCO3 solution (5 μL). Precursor stock solution was prepared by dissolving fallypride precursor (4 mg) in a mixture of MeCN and thexyl alcohol (1:1 v/v, 100 μL). A stock solution for dilution of the crude product prior to collection was prepared from a mixture of MeOH and DI water (9:1, v/v, 500 μL). These solutions were loaded into individual reagent vials connected to dispensers.
To perform the on-chip synthesis, a 2 μL droplet of [18F]fluoride solution (~7.4 MBq; ~0.2 mCi) was first loaded onto the chip and spontaneously transported to the reaction site. The microfluidic chip was heated to 105°C for 1 min to evaporate the solvent and leave a dried residue of the [18F]tetrabutylammonium fluoride ([18F]TBAF) complex at the reaction site. It was found that the typical azeotropic distillation process (i.e. addition and evaporation of MeCN) to remove residual moisture was not needed.
Next, a 1 μL droplet of fallypride precursor solution was deposited at another loading site and was spontaneously transported to the reaction site, where it dissolved the dried residue. Then, another 1 μL droplet of fallypride precursor solution was deposited and transported the same way. The chip was heated to 110°C and held for 7 min to accomplish the radiofluorination reaction. Then, ten 1 μL droplets of collection solution were sequentially deposited at a different reagent loading site and spontaneously moved to reaction site to dilute the resulting crude reaction mixture. Afterwards, the diluted droplet was transferred into the collection vial. The collection process was repeated 5x to minimize residue on the chip. A schematic of the on-chip process is shown inFigure 4 .
A [18F]fluoride stock solution was prepared by mixing [18F]fluoride/[18O]H2O (100 μL, ~370 MBq; ~10 mCi) with 75 mM TBAHCO3 solution (5 μL). Precursor stock solution was prepared by dissolving fallypride precursor (4 mg) in a mixture of MeCN and thexyl alcohol (1:1 v/v, 100 μL). A stock solution for dilution of the crude product prior to collection was prepared from a mixture of MeOH and DI water (9:1, v/v, 500 μL). These solutions were loaded into individual reagent vials connected to dispensers.
To perform the on-chip synthesis, a 2 μL droplet of [18F]fluoride solution (~7.4 MBq; ~0.2 mCi) was first loaded onto the chip and spontaneously transported to the reaction site. The microfluidic chip was heated to 105°C for 1 min to evaporate the solvent and leave a dried residue of the [18F]tetrabutylammonium fluoride ([18F]TBAF) complex at the reaction site. It was found that the typical azeotropic distillation process (i.e. addition and evaporation of MeCN) to remove residual moisture was not needed.
Next, a 1 μL droplet of fallypride precursor solution was deposited at another loading site and was spontaneously transported to the reaction site, where it dissolved the dried residue. Then, another 1 μL droplet of fallypride precursor solution was deposited and transported the same way. The chip was heated to 110°C and held for 7 min to accomplish the radiofluorination reaction. Then, ten 1 μL droplets of collection solution were sequentially deposited at a different reagent loading site and spontaneously moved to reaction site to dilute the resulting crude reaction mixture. Afterwards, the diluted droplet was transferred into the collection vial. The collection process was repeated 5x to minimize residue on the chip. A schematic of the on-chip process is shown in
