Convenient PET-tracer production via SuFEx F-fluorination of nanomolar precursor amounts.

Recently, a protocol for radiolabeling of aryl fluorosulfates ("SuFEx click radiolabeling") using ultrafast F/F isotopic exchange has been reported. Although promising, the original procedure turned out to be rather inefficient. However, systematic optimization of the reaction parameters allowed for development of a robust method for SuFEx radiolabeling which obviates the need for azeotropic drying, base addition and HPLC purification. The developed protocol enabled efficient F-fluorination of low nanomolar amounts of aryl fluorosulfates in highly diluted solution (micromolar concentrations). It was successfully used to prepare a series of 29 F-fluorosulfurylated phenols - including modified ezetimibe, α-tocopherol and etoposide, the two tyrosine derivatives Boc-Tyr([F]FS)-OMe and H-Tyr([F]FS)-OMe, the FAP-specific ligand [F]FS-UAMC1110, and the DPA-714 analog [F]FS-DPA - in fair to excellent yields. Preliminary evaluation demonstrated sufficient in vivo stability of radiofluorinated electron rich or neutral {Boc-Tyr([F]FS)-OMe), H-Tyr([F]FS)-OMe and [F]FS-DPA} aryl fluorosulfates. Furthermore, [F]FS-DPA was identified as a promising tracer for visualization of TSPO expression.