Microfluidic radiosynthezier chip

Droplet-based microfluidic radiosynthesizer for on-demand synthesis of labeled radiopharmaceuticals

“Current equipment and methods for preparation of radiopharmaceuticals for positron emission tomography (PET) are expensive and best suited for large-scale multi-doses batches. Microfluidic radiosynthesizers have been shown to provide an economic approach to synthesize these compounds in smaller quantities, but can also be scaled to clinically-relevant levels. Batch microfluidic approaches, in particular, offer significant reduction in system size and reagent consumption. Here we show a simple and rapid technique to concentrate the radioisotope, prior to synthesis in a droplet-based radiosynthesizer, enabling production of clinically-relevant batches of [18F]FET and [18F]FBB. The synthesis was carried out with an automated synthesizer platform based on a disposable Teflon-silicon surface-tension trap chip. Up to 0.1 mL (4 GBq) of radioactivity was used per synthesis by drying cyclotron-produced aqueous [18F]fluoride in small increments directly inside the reaction site. Precursor solution (10 µL) was added to the dried [18F]fluoride, the reaction chip was heated for 5 min to perform radiofluorination, and then a deprotection step was performed with addition of acid solution and heating. The product was recovered in 80 µL volume and transferred to analytical HPLC for purification. Purified product was formulated via evaporation and resuspension or a micro-SPE formulation system. Quality control testing was performed on 3 sequential batches of each tracer. The method afforded production of up to 0.8 GBq of [18F]FET and [18F]FBB. Each production was completed within an hour. All batches passed quality control testing, confirming suitability for human use. In summary, we present a simple and efficient synthesis of clinically-relevant batches of [18F]FET and [18F]FBB using a microfluidic radiosynthesizer. This work demonstrates that the droplet-based micro-radiosynthesizer has a potential for batch-on-demand synthesis of 18F-labeled radiopharmaceuticals for human use.


Microfluidic radiosynthezier chip

“(A) Photographs of a disposable reaction chip (left) and automated droplet synthesizer (right). (B) Top view schematic of dispenser arrangement for a multi-step droplet synthesis. (C) Simplified schematic showing position of rotating platform during various steps of a typical radiosynthesis (reagent addition, heating, and collection of crude product).” Reproduced under Creative Commons Attribution 4.0 International License. from Lisova et al. Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use. Sci. Rep., 11, 20636 (2021)..

Figures and the abstract are reproduced from Lisova, K., Wang, J., Hajagos, T.J. et al. Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use. Sci Rep 11, 20636 (2021). under Creative Commons Attribution 4.0 International License

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Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use