Acyl [¹⁸F]fluorides as novel synthons for radiofluorination

Objectives Current methods for delivery, extraction, and reformulation of [¹⁸F]fluoride from proton-irradiated ¹⁸O-enriched water are far from ideal. We have developed gaseous acyl [¹⁸F]fluorides as novel synthons that offer the ability to transfer [¹⁸F]fluoride through gas lines in an anhydrous form.

Methods [¹⁸F]fluoride in ¹⁸O-enriched water was trapped on an anion-exchange cartridge (MP-64, 40 mg) maintained at 70 °C. The cartridge was rinsed with acetone and dried under nitrogen. Acetic or propionic anhydride were added to the cartridge and allowed to react for 3 min, producing acetyl [¹⁸F]fluoride (AcF, Bp = 21 °C) or propanoyl [¹⁸F]fluoride (PrF, Bp = 43 °C), respectively. The gaseous acyl [¹⁸F]fluorides were swept by nitrogen from the MP-64 cartridge through an empty cartridge and two cartridges filled with Porapak-Q medium (900 mg each) maintained at 30-40 °C. The product was then transported through polypropylene (PP) tubing to a distant radiochemistry location. The acyl [¹⁸F]fluorides were efficiently trapped in acetonitrile and other polar organic solvents for subsequent radiofluorinations.

Results The unoptimized yields of purified acyl [¹⁸F]fluorides were 60-75% uncorrected. Radiochemical purity was confirmed as >99% by GC-FID which is sensitive to radioactivity. Chemical purity was also >99% as shown by GC-FID. [¹⁸F]AcF was transported through 15 m of PP tubing (0.79 mm ID) with <0.9% adsorbance to the tubing. Adsorbance of [¹⁸F]PrF to PP tubing was significantly higher (3.8% over 15 m). ¹⁸F-fluorination of the mannose triflate FDG precursor in acetonitrile at 80 °C was >90% after addition of 10 mg tetraethylammonium bicarbonate to release the [¹⁸F]fluoride into solution.

Conclusions ¹⁸F-labeled acyl fluorides were efficiently produced by a method that lends itself to automation. The anhydrous nature of acyl [¹⁸F]fluorides may be advantageous for water-sensitive reactions. Furthermore, their gaseous form may inspire new paradigms for distribution and utilization of [¹⁸F]fluoride. Additional applications for use of acyl [¹⁸F]fluorides for radiosynthesis are ongoing.