Automated concentration of [18F]fluoride into microliter volumes

Abstract

Concentration of [F]fluoride has been mentioned in literature, however, reports have lacked details about system designs, operation, and performance. Here, we describe in detail a compact, fast, fully-automated concentration system based on a micro-sized strong anion exchange cartridge. The concentration of radionuclides enables scaled-up microfluidic synthesis. Our system can also be used to provide highly concentrated [F]fluoride with minimal water content. We demonstrate how the concentrator can produce varying concentrations of [F]fluoride for the macroscale synthesis of N-boc-5-[F]fluoroindole without an azeotropic drying process, while enabling high starting radioactivity. By appropriate choice of solid-phase resin, flow conditions, and eluent solution, we believe this approach can be extended beyond [F]fluoride to other radionuclides.

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

“…In this work the synthesis of [ 18 F]FET was adapted to an automated microdroplet synthesis platform (Wang et al 2017). The product was obtained in high RCY of up to 55 ± 7% (n = 4, decay-corrected) after purification, in sufficient quantities to perform a demonstration of a multi-animal dynamic PET imaging study, and could readily be scaled to higher amounts using radionuclide concentration methods (Chao et al 2018a). Synthesis time was shorter than conventional approaches, precursor consumption was reduced by two orders of magnitude, and the synthesis could be performed with a very small apparatus.…”

Multi-GBq production of the radiotracer [18F]fallypride in a droplet microreactor

“…A detailed report of the design and operation of the [ 18 F] uoride concentrator, operated here in the "direct loading" conguration, was recently published. 19 Briey, the system relies on a miniature SAX cartridge. Upstream of the concentrator, we incorporated a simple module for strong cation exchange (SCX) cartridge ltration of the initial [ 18 F]uoride solution to eliminate contaminants and small particles that could potentially interfere with trapping on the micro-cartridge (ESI Section 11 †).…”

“…The micro-cartridges for the radionuclide concentrator were fabricated by a different method than our previous report. 19 Due to the high cost and limited re-usability of commercially-packed cartridges (with $4 mL bed volume and $2 mg of resin), we opted to pack the resin ourselves into short segments of tubing (ESI Section 2 †). Cartridges were packed with one of several different resins: Bio-Rad AG-MP1 (200-400 mesh size; Bio Rad, Hercules, CA, USA), resin from Sep-Pak Plus QMA Light Cartridges (37-55 mm particle size; Waters Corporation, Milford, MA, USA), or resin from Oasis MAX Plus short cartridges (30 mm particle size; Waters Corporation).…”

“…Recently, our lab developed a fullyautomated standalone [ 18 F]uoride concentrator based on a miniaturized strong anion exchange (SAX) cartridge that can trap [ 18 F]uoride from 1 mL starting volume and efficiently release it into an output volume of 12.4 mL in 10 min. 19 Leveraging the latter approach due to its speed and versatility, we study here, for the rst time, the performance of droplet-based radiosynthesis starting with 10 s of GBq [100 s of mCi] activity and explore the potential of compact droplet-based radiochemistry platforms to be used in clinically-relevant applications. To accomplish this, we developed a method of rapidly transferring the concentrated radionuclide to the passive-transport-based droplet synthesizer with near quantitative efficiency, and furthermore optimized the synthesis conditions based on the elution conditions needed to efficiently concentrate the [ 18 F]uoride.…”

A novel multi-reaction microdroplet platform for rapid radiochemistry optimization

“…Due to success in synthesizing other tracers on this and similar microuidic platforms, 9,15,22 we expect this platform to be applicable to the development and optimization of a wide range of PET tracers and other radiopharmaceuticals. In other work, we have shown the ability to increase the scale of dropletbased reactions by pre-concentrating the radioisotope, 23 providing a route to immediately transition from low-activity optimization runs to high-activity production runs using the exact same droplet reaction geometry and synthesis process. Thus, microdroplet reactions are not only a useful tool during the optimization phase, but also can produce sufficient quantity of tracers for preclinical or even clinical studies.…”