In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. K₂CO₃) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesized that these limitations could be addressed through the development of alternate techniques for preparing [¹⁸F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [¹⁸F]fluoride from ion exchange cartridges. The new procedures are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.

A one-pot two-step synthesis of 6-[¹⁸F]fluoro-l-DOPA has been developed, involving Cu-mediated radiofluorination of the corresponding pinacol boronate ester precursor, and validated for production of doses for human use.

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia and macrophages. AZ683 has high affinity for CSF1R (K_i = 8 nM; IC₅₀ = 6 nM) and >250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [¹¹C]AZ683 and initial evaluation of its use in CSF1R PET. [¹¹C]AZ683 was synthesized by ¹¹C-methylation of the desmethyl precursor with [¹¹C]MeOTf in 3.0% non-corrected activity yield (based upon [¹¹C]MeOTf), >99% radiochemical purity and high molar activity. Preliminary PET imaging with [¹¹C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation.

This report describes a Pd-mediated C–H radiofluorination of 8-methylquinoline derivatives with no-carrier-added Ag[ ¹⁸ F]F. Fluorination of 10 examples in up to 21% RCY and high molar activity is reported, as well as automation of the process in a radiochemistry synthesis module.

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases and, in this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high specific activity. Preliminary PET imaging with [11C]AZ683 revealed no brain uptake in rodents and nonhuman primates suggesting that [11C]AZ683 is a poor candidate for imaging neuroinflammation, but that it could still be useful for peripheral imaging of inflammation.