[18F]F2 – New production methods and applications

Abstract

Fluorine-18 is a positron emitting radioisotope. It has a half-life of 109.8 min, a simple decay profile and low positron energy as a result of which properties fluorine-18 is an excellent candidate for use in the production of tracers for positron emission tomography (PET). Radiochemistry with fluorine-18 starts from the production of the radioactive isotope, which is then used for the labelling of bioactive molecules. The labelling can be done by nucleophilic or electrophilic methods. Nucleophilic 18F-fluorination, using [18F]F-, is the most popular approach due to the effective production method. Production of [18F]F2 is more challenging and is one of the limiting factors for the use of electrophilic 18F-fluorination. Production of [18F]F2 requires the addition of carrier F2, which reduces the molar activity of the product. The electrophilic labelling method that gives the highest molar activity utilizes a high voltage discharge in the production of [18F]F2.

In this study, the first of the methods developed for the production of [18F]F2 replaces the high voltage discharge with a milder, more reliable excitation source i.e., high energy photons. In a second method, the toxic, very reactive F2 gas used as a carrier is replaced by the very inert SF6 gas. In addition, new applications of [18F]F2 based labelling syntheses were developed. [18F]F2 and its derivatives were used for stereoselective 18F-fluorination, for the production of [18F]-4-fluorosydnone, a new reagent for click chemistry as well as, for the production of 6-[18F]fluoro-marsanidine, a PET tracer candidate for brain α2A-adrenoceptors imaging.

Both methods developed for the production of [18F]F2 resulted in the production of the desire product in low yield and with moderated molar activity (Am). Stereoselective 18Ffluorination resulted in high yield and products in high enantiomeric excess. [18F]-4- fluorosydnone, was successfully used for a click reaction, resulting in rapid complete cycloaddition. 6-[18F]fluoro-marsanidine was synthetized with a quality sufficient for preclinical evaluation. However, rapid in vivo metabolism limits its usefulness for brain α2Aadrenoceptor imaging in rodents.