Convenient PET-tracer production via SuFEx 18F-fluorination of nanomolar precursor amounts

Abstract

Recently, a protocol for radiolabeling of aryl fluorosulfates (“SuFEx click radiolabeling”) using ultrafast ¹⁸F/¹⁹F 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 ¹⁸F-fluorination of low nanomolar amounts of aryl fluorosulfates in highly diluted solution (micromolar concentrations). It was successfully used to prepare a series of 29 ¹⁸F-fluorosulfurylated phenols – including modified ezetimibe, α-tocopherol and etoposide, the two tyrosine derivatives Boc-Tyr([¹⁸F]FS)-OMe and H-Tyr([¹⁸F]FS)-OMe, the FAP-specific ligand [¹⁸F]FS-UAMC1110, and the DPA-714 analog [¹⁸F]FS-DPA – in fair to excellent yields. Preliminary evaluation demonstrated sufficient in vivo stability of radiofluorinated electron rich or neutral {Boc-Tyr([¹⁸F]FS)-OMe), H-Tyr([¹⁸F]FS)-OMe and [¹⁸F]FS-DPA} aryl fluorosulfates. Furthermore, [¹⁸F]FS-DPA was identified as a promising tracer for visualization of TSPO expression.

Walter, N.; Bertram, J.; Drewes, B.; Bahutski, V.; Timmer, M.; Schütz, M. B.; Krämer, F.; Neumaier, F. (Corresponding author); Endepols, H.; Neumaier, B. (Corresponding author); Zlatopolskiy, B. D.

Convenient PET-tracer production via SuFEx ¹⁸F-fluorination of nanomolar precursor amounts

European Journal of Medicinal Chemistry, 2022, Volume 237