On-chip pre-concentration and complexation of [18F]fluoride ions via regenerable anion exchange particles for radiochemical synthesis of Positron Emission Tomography tracers

Microfluidic approaches have demonstrated a relevant impact on radiochemical reactions involving Positron Emission Tomography (PET) nuclides, due to shorter reaction times and smaller precursor quantities. However, little attention has been given to the integration of the initial pre-concentration and drying of radioactive [18F]fluoride ions, required for the labeling of radiotracer compounds. In this work we report the design, fabrication and implementation of a glass microfluidic device filled with recyclable anion exchange particles for the repeated recovery of [18F] and [19F]fluoride ions. The device was first tested with non radioactive [19F]fluoride ions and it was shown to repeatedly trap and elute >95% fluoride over 40 successive experimental runs with no decrease in efficiency. The same device was then tested for the trapping and release of [18F]fluoride ions over 20 experiments with no measurable decrease in performance. Finally, the [18F]fluoride ions were eluted as a K18F/K2.2.2 complex, dried by repeated dissolution in acetonitrile and evaporation of residual water, and reacted with ethyl ditosylate (EtDT) leading to the desired product ([18F]fluoroethyltosylate) with 96 ± 3% yield (RCY). The overall time needed for conditioning, trapping, elution and regeneration was less than 6 min. This approach will be of great benefit towards an integrated platform able to perform faster and safer radiochemical synthesis on the micro-scale.