High yield and high specific activity synthesis of [18F]fallypride in a batch microfluidic reactor for micro-PET imaging.

[(18)F]fallypride was synthesized in a batch microfluidic chip with a radiochemical yield of 65 ± 6% (n = 7) and an average specific activity of 730 GBq µmol(-1) (20 Ci µmol(-1)) (n = 4). Specific activity was ~2-fold higher than [(18)F]fallypride synthesized in a macroscale radiosynthesizer, despite starting with significantly less radioactivity, and thus safer conditions, in the microchip.

Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip.

Radiotracer synthesis is an ideal application for microfluidics because only nanogram quantities are needed for positron emission tomography (PET) imaging. Thousands of radiotracers have been developed in research settings but only a few are readily available, severely limiting the biological problems that can be studied in vivo via PET. We report the development of an electrowetting-on-dielectric (EWOD) digital microfluidic chip that can synthesize a variety of (18)F-labeled tracers targeting a range of biological processes by confirming complete syntheses of four radiotracers: a sugar, a DNA nucleoside, a protein labelling compound, and a neurotransmitter. The chip employs concentric multifunctional electrodes that are used for heating, temperature sensing, and EWOD actuation. All of the key synthesis steps for each of the four (18)F-labeled tracers are demonstrated and characterized with the chip: concentration of fluoride ion, solvent exchange, and chemical reactions. The obtained fluorination efficiencies of 90-95% are comparable to, or greater than, those achieved by conventional approaches.