Continuous-flow synthesis of [11C]raclopride, a positron emission tomography radiotracer, on a microfluidic chip

C-11-labelled radiotracers such as [C-11]raclopride are produced in a process that can take between 45 and 60 min to complete. These conventional approaches can consume upwards of 75% of the C-11 (t(1/2) = 20 min) due to radioactive decay alone, even more if synthesis losses are considered. To compensate, a large starting quantity of radioactive precursors such as [C-11]methyl iodide is required to produce an adequate amount of the tracer for injection. In this investigation, a continuous-flow microchip is explored for the purpose of synthesizing C-11 radiotracers in a shorter time by exploiting the favorable reaction kinetics of using smaller reaction volumes. To enhance the mixing of reagents within the microchannel, a micromixer "loop" design was used in fabricating various polydimethylsiloxane chip styles. With a loop design implemented in an abacus-style chip for the production of nonradioactive raclopride, shorter reaction times, reduced precursor use, and improved yields were possible when compared with the use of a simple serpentine design (no loop-style chip). However, when performing the equivalent radiochemical reaction, the results were not as favorable. Using the loop design in a full loop-style chip, parameters such as premixing the reagents, reducing flow rate, and varying reagent concentrations were explored to improve the yields of [C-11]raclopride (in terms of relative radioactivity) formed. The full loop chip design produced the best results, and future work will see the polydimethylsiloxane prototype chip design translated into a glass chip for further optimization.