Automated [¹⁸F]F₂ gas production from [¹⁸F]fluoride ion

Objectives The objective of this work is to increase the availability of high specific activity [¹⁸F]F₂ gas for radiotracer preparation through the development of an automated production system. The two step process entails the production of [¹⁸F]fluoromethane (CH₃¹⁸F) from aqueous [¹⁸F]fluoride ion (¹⁸F^-) with subsequent conversion to [¹⁸F]F₂ gas by the Bergman and Solin (1997) electric discharge method.

Methods A device was built for automated preparation of CH₃¹⁸F including concentration of ¹⁸F^-, elution with aqueous DMSO and reaction with aryl trimethylammonium salts at 175° C. A second device was built to receive the CH₃¹⁸F for electric discharge conversion to [¹⁸F]F₂ gas. The % of [¹⁸F]F₂ gas produced was determined by trapping in solid KI. The reactivity of the [¹⁸F]F₂ was determined by reaction with FDOPA precursor in Freon-11 and EF5 precursor in TFA. Products were characterized by HPLC comparison with standards. Different variables (amount of nonradioactive [¹⁸F]F₂ gas, spark time (10 sec vs. 3 min), current voltage applied (up to 0.4mA), and size of spark chamber) were evaluated to determine the ideal conditions for [¹⁸F]F₂ gas production.

Results Reaction of aryl trimethylammonium salts with aqueous ¹⁸F^- gave consistently high yields (85-95%) of CH₃¹⁸F. The % yield of [¹⁸F]F₂ gas produced ranges up to 50% based on CH₃¹⁸F activity. [¹⁸F]FDOPA and [¹⁸F]EF5 labeling was confirmed on RP-HPLC.

Conclusions A fully functional automated [¹⁸F]F₂ production system has been developed. This system can be used multiple times in one day to produce [¹⁸F]F₂ on demand without intervention. Further optimization is warranted to obtain an improved [¹⁸F]F₂ yield.

Research Support This research was supported in part by the Office of Biological and Environmental Research, US DOE under grant no DE-FG02-08ER64699 and a grant from Varian Byosynergy