Automated preparation of [18F]AFP and [18F]BFP: Two novel bifunctional 18F-labeling building blocks for Huisgen-click

•The development of two novel 18F-building blocks for radiolabeling is described.•These show favorable properties like logP/D, solubility and in vitro stability.•Precursors based on spiro compounds allow a convenient separation using cartridges.•The automated module synthesis proceeded 40 min and delivered high RCY.•An application using the bioorthogonal Cu-AAC under mild conditions is possible.

A bioorthogonal labeling approach based on the Huisgen-click reaction including the one-step radiosynthesis of two novel versatile and bifunctional labeling building blocks ([18F]AFP) [18F]12 and ([18F]BFP) [18F]6 with the PET radionuclide fluorine-18 is described. Optimized reaction conditions for the fully automated synthesis procedure using the TRACERlab FxFN module gave both piperazine derivatives [18F]6 and [18F]12 with radiochemical yields of 31 ± 9% (S.D., n = 8, d.c.) and 29 ± 5% (S.D., n = 19, d.c.), respectively, within 40 min synthesis time and high specific activities after convenient purification using silica gel cartdridges. First biological studies of both building blocks revealed a remarkable in vitro stability in rat blood as well as rat plasma over more than 60 min. Sample ligation reactions of [18F]6 and [18F]12 with azide and alkyne functionalized amino acid derivatives yielded the corresponding labeled triazoles in good to high RCYs. Moreover, the azide functionalized peptide 17, which is highly affine to the EphB2 receptor due to its SNEW sequence, was synthesized and successfully radiolabeled with [18F]BFP [18F]6 under relatively mild conditions yielding the corresponding triazolyl-peptide [18F]18.

Graphical abstractTwo capable and universally applicable fluorine-18 containing building blocks were prepared in a remotely controlled module synthesis for the radiolabeling of azide or alkyne functionalized amino acids or peptides under mild conditions with the bioorthogonal Huisgen click reaction.Figure optionsDownload full-size imageDownload as PowerPoint slide