Conventional nucleophilic radiofluorination requires azeotropic drying to generate reac-tive [18F]fluoride, introducing time delays and activity losses. [18F]Fluoride relay reagents such as [18F]triflyl fluoride ([18F]TfF) and [18F]ethenesulfonyl fluoride ([18F]E=SF) have re-cently emerged as efficient alternatives that bypass this step. Here, we introduce [18F]ethanesulfonyl fluoride ([18F]E-SF) as a new relay reagent and benchmark its produc-tion and radiolabelling performance against [18F]TfF and [18F]E=SF.
[18F]E-SF was prepared from commercially available 2,4,6-trichlorophenyl-1-ethanesulfonate (TCP-ethane) using a microlitre-scale radiofluor-ination approach, enabling direct distillation and SPE trapping of the product. Under op-timised conditions, [18F]E-SF was obtained in 76 ± 23% RCY (n=6), compared with 27 ± 6% (n=2) for [18F]E=SF and up to 97 ± 2% (n=3) for [18F]TfF using an optimized literature-based protocol. Subsequent model labelling reactions demonstrated effective aliphatic nucleo-philic substitution to [18F]fluoroethyl tosylate ([18F]FEtOTs) and aromatic nucleophilic sub-stitution to [18F]fluorobenzaldehyde with high radiochemical conversion.
These results establish [18F]E-SF as a robust and operationally simple relay reagent with high production yields from a commercial available precursor. It is compatible with SPE trapping and achieves production yields comparable to [18F]E=SF and [18F]TfF respective-ly, warranting future automated production for supporting the potential use of [18F]E-SF in streamlined and decentralised 18F-labelling workflows.

Conventional nucleophilic radiofluorination requires azeotropic drying to generate reac-tive [18F]fluoride, introducing time delays and activity losses. [18F]Fluoride relay reagents such as [18F]triflyl fluoride ([18F]TfF) and [18F]ethenesulfonyl fluoride ([18F]E=SF) have re-cently emerged as efficient alternatives that bypass this step. Here, we introduce [18F]ethanesulfonyl fluoride ([18F]E-SF) as a new relay reagent and benchmark its produc-tion and radiolabelling performance against [18F]TfF and [18F]E=SF.
[18F]E-SF was prepared from commercially available 2,4,6-trichlorophenyl-1-ethanesulfonate (TCP-ethane) using a microlitre-scale radiofluor-ination approach, enabling direct distillation and SPE trapping of the product. Under op-timised conditions, [18F]E-SF was obtained in 76 ± 23% RCY (n=6), compared with 27 ± 6% (n=2) for [18F]E=SF and up to 97 ± 2% (n=3) for [18F]TfF using an optimized literature-based protocol. Subsequent model labelling reactions demonstrated effective aliphatic nucleo-philic substitution to [18F]fluoroethyl tosylate ([18F]FEtOTs) and aromatic nucleophilic sub-stitution to [18F]fluorobenzaldehyde with high radiochemical conversion.
These results establish [18F]E-SF as a robust and operationally simple relay reagent with high production yields from a commercial available precursor. It is compatible with SPE trapping and achieves production yields comparable to [18F]E=SF and [18F]TfF respective-ly, warranting future automated production for supporting the potential use of [18F]E-SF in streamlined and decentralised 18F-labelling workflows.