Green and efficient synthesis of the radiopharmaceutical [¹⁸F]FDOPA using a microdroplet reactor

From an efficiency standpoint, microdroplet reactors enable significant improvements in the preparation of radiopharmaceuticals due to the vastly reduced reaction volume. To demonstrate these advantages, we adapt the conventional (macroscale) synthesis of the clinically-important positron-emission tomography tracer [¹⁸F]FDOPA, following the nucleophilic diaryliodonium salt approach, to a newly-developed ultra-compact microdroplet reaction platform. In this first microfluidic implementation of [¹⁸F]FDOPA synthesis, optimized via a high-throughput multi-reaction platform, the radiochemical yield (non-decay-corrected) was found to be comparable to macroscale reports, but the synthesis consumed significantly less precursor and organic solvents, and the synthesis process was much faster. In this initial report, we demonstrate the production of [¹⁸F]FDOPA in 15 MBq [400 μCi] amounts, sufficient for imaging of multiple mice, at high molar activity.