Magnetic Droplet Microfluidics as a Platform for the Concentration of [¹⁸F]Fluoride and Radiosynthesis of Sulfonyl [¹⁸F]Fluoride

The radioisotope ¹⁸F is often considered the best choice for positron emission tomography (PET) owing to its desirable chemical and radiochemical properties. However, nucleophilic ¹⁸F-fluorination of large, water-soluble biomolecules, based on C-F bond formation, has traditionally been difficult. Thus, several aqueous fluorination approaches that offer significant versatility in radiopharmaceutical synthesis with sensitive targeting vectors have been developed. Furthermore, because ¹⁸F decays rapidly, production of these ¹⁸F-labeled compounds requires an automated process to reduce production time, reduce radiation exposure, and minimize losses due to the transfer of reagents during tracer synthesis. Herein, we report the use of magnetic droplet microfluidics (MDM) as a means to concentrate [¹⁸F]fluoride from the cyclotron target solution, followed by the synthesis of an ¹⁸F-labeled compound on a microfluidic platform. Using this method, we have demonstrated ¹⁸F preconcentration in a small-volume droplet through the use of anion exchanging magnetic particles. By using MDM, the preconcentration step took approximately 5 min, and the [¹⁸F]fluoride solution was preconcentrated by 15-fold. After the preconcentration step, an ¹⁸F-labeling reaction was performed on the MDM platform using the S-F bond formation in aqueous conditions to produce an arylsulfonyl [¹⁸F]fluoride compound which can be used as a prosthetic group to label PET targeting ligands. The high radiochemical purity of 95 ± 1% was comparable to the 96% previously reported using a conventional method. In addition, when MDM was used, the total synthesis time was improved to 15 min with lower reagent volumes (50-60 μL) used.