Optimization of nucleophilic 18F radiofluorinations using a microfluidic reaction approach

Pascali, G; Matesic, L; Collier, TL; Wyatt, NA; Fraser, BH; Pham, TQ; Salvadori, PA; Gueguric, I

Optimization of nucleophilic 18F radiofluorinations using a microfluidic reaction approach

Date

2014-07-31

Authors

Publisher

Nature Publishing Group

Abstract

Microfluidic techniques are increasingly being used to synthesize positron-emitting radiopharmaceuticals. Several reports demonstrate higher incorporation yields, with shorter reaction times and reduced amounts of reagents compared with traditional vessel-based techniques. Microfluidic techniques, therefore, have tremendous potential for allowing rapid and cost-effective optimization of new radiotracers. This protocol describes the implementation of a suitable microfluidic process to optimize classical 18F radiofluorination reactions by rationalizing the time and reagents used. Reaction optimization varies depending on the systems used, and it typically involves 5–10 experimental days of up to 4 h of sample collection and analysis. In particular, the protocol allows optimization of the key fluidic parameters in the first tier of experiments: reaction temperature, residence time and reagent ratio. Other parameters, such as solvent, activating agent and precursor concentration need to be stated before the experimental runs. Once the optimal set of parameters is found, repeatability and scalability are also tested in the second tier of experiments. This protocol allows the standardization of a microfluidic methodology that could be applied in any radiochemistry laboratory, in order to enable rapid and efficient radiosynthesis of new and existing [18F]-radiotracers. Here we show how this method can be applied to the radiofluorination optimization of [18F]-MEL050, a melanoma tumor imaging agent. This approach, if integrated into a good manufacturing practice (GMP) framework, could result in the reduction of materials and the time required to bring new radiotracers toward preclinical and clinical applications. © 2014, Nature Publishing Group

Keywords

Fluids, Synthesis, Positron reactions, Radiopharmaceuticals, Reagents, Experiment results, Neoplasms, Tracer techniques

Citation

Pascali, G., Matesic, L., Collier, T. L., Wyatt, N., Fraser, B. H., Pham, T. Q., Salvadori, P. A., & Greguric, I. (2014). Optimization of nucleophilic 18F radiofluorinations using a microfluidic reaction approach. Nature Protocols, 9(9), 2017-2029. doi:10.1038/nprot.2014.137