¹⁸F-fluorophenylation: Method for radiolabelling of peptides and amino acids in aqueous media

Despite all efforts in peptide labeling there is a still lack in suitable methods. Reaction of 4-[F-18]fluorobenzenediazonium chloride with a cysteinyl residue of a peptide provides a route for the no carrier added (n.c.a.) F-18-radiolabeling of peptides in aqueous media. Furthermore radiolabeled conjugates of cysteine might be interesting compounds for tumor imaging with PET. 4-[F-18]fluoroaniline was prepared in >60% radiochemical yield by reacting 1,4-dinitrobenzene with n.c.a. [F-18]fluoride in a microwave oven and subsequent catalytic reduction. After diazotization with NaNO₂ and addition of ammonia or hydroxylamine solution cysteine or glutathione as a model peptide (GSH) were reacted with the generated diazonium cation. The reaction of 4-[F-18]fluorobenzenediazonium ion with 0.1M cysteine solution resulted in almost quantitative yields of S-4-[F18]fluorophenyldiazocysteine which was converted by UV irradiation to S-4-[F-18]fluorophenylcysteine (45%, based on 4-[F-18]fluoroaniline). S-4-[F-18]fluorophenyl-L-cysteine showed rapid and high uptake in HT29 cells and thus might be interesting for tumor imaging with PET. 75% of S-4-[F-18]fluorophenyldiazo-GSH were obtained for a GSH concentration of 1.3 mM, nearly quantitative yields at higher concentrations (based on 4-[F-18]fluoroaniline). UV-irradiation ends up in S-[F-18]fluorophenyl-GSH in good yields. In the same way the [F-18]fluorophenylcysteinyl group serves as a substitute for homophenylalanine in labeled peptides.