A microfluidic chip-based synthesis of carbon-11 radiotracers for the purpose of PET imaging

A microchip-based technique was developed for the radiolabeling process of positron emission tomography (PET) radiotracers using C–11. Due to C–11’s short half-life (20.4 min) it is beneficial to develop a rapid and efficient synthesis that can be done while the patient is waiting. The investigation began with the non-radioactive synthesis of raclopride ((2S)-(-)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-6-hydroxy-2-methoxybenzamide), a compound used to study dopamine receptors. The reaction was optimized on the microchip achieving 2-times the yields using ~1/20th the precursor amounts and ~1/5th the reaction time compared to the conventional method. Consequently, optimal parameters were applied to the radiolabeling synthesis of L-[methyl-11C]-methionine achieving 100% relative activities while the [11C]raclopride synthesis resulted in lower relative activities. Therefore reaction conditions were investigated and a computational mass transfer study showed that the reaction kinetics of the radiolabeling process must be considered for the microchip design.