Methods for the radiolabeling molecules of interest with [18F]-fluoride need to be rapid, convenient, and efficient. Numerous [18F]-labeled prosthetic groups, e.g., N-succinimidyl 4 [18F]-fluorobenzoate ([18F]-SFB), 4-azidophenacyl-[18F]-fluoride ([18F]-APF), and 1-(3-(2-[18F]fluoropyridin-3-yloxy)propyl)pyrrole-2,5-dione ([18F]-FpyMe), for conjugating to biomolecules have been developed. As the synthesis of these prosthetic groups usually requires multistep procedures, there is still a need for direct methods for the nucleophilic [18F]-fluorination of biomolecules. We report here on the development of a procedure based on the trimethylammonium (TMA) leaving group attached to an aromatic ring and activated with different electron-withdrawing groups (EWGs). A series of model compounds containing different electron-withdrawing substituents, a trimethylammonium leaving group, and carboxylic functionality for subsequent coupling to peptides were designed and synthesized. The optimal model compound, 2-cyano-4-(methoxycarbonyl)-N,N,N-trimethylbenzenaminium trifluoromethanesulfonate, was converted to carboxylic acid and coupled to peptides. The results of the one-step [18F]-fluorination of tetrapeptides and bombesin peptides show that the direct 18F-labeling of peptides is feasible under mild conditions and in good radiochemical yields.

SummaryCompared to homoaromatic and aliphatic nucleophilic radiofluorinations, only few references can be found in the literature describing nucleophilic substitutions with studied include the influence of the position of the leaving group at the pyridine ring, as well as the quantity of the precursor used, the type of activation (conventional heating, microwave irradiation), the solvent, the temperature and the reaction time. Using the corresponding nitro precursor, high yields were obtained at the 2-position (94% yield) using microwaves (100 W) for 2 min in DMSO. Good yields (up to 72%) were observed at the 4-position using the same conditions while practically no reaction was observed at the 3-position. About 60% yield was also obtained at both the 2-and 4-position

No abstract

No abstract

SummaryThis paper describes the radiosynthesis of 3-

SummaryThe scope of the nucleophilic aromatic ortho-fluorinations from the corresponding ortho-halonitrobenzene precursors (halo-to-fluoro substitutions) with no-carrier-added benzene, chosen as a model reaction. The parameters studied include the influence of the leaving group in the ortho position of the phenyl ring (-Cl, -Br, -l), the quantity of precursor used, the type of activation (conventional heating or microwave irradiations), the solvent, the temperature and the reaction time. The iodo-precursor was completely unreactive and the bromo-precursor gave only low incorporation (510%) in the optimal conditions used (conventional heating at 1458C or microwave activation, 100 W for 120 s). Only the chloroprecursor was found reactive in the conditions described above and up to 70% yield was observed for the formation of ortho-In all the experiments, the unwanted ortho-[ 18 F]fluoro-halobenzenes, potentially resulting from the nitro-to-fluoro substitution, could not be detected. These results will be applied for the radiosynthesis of 5-[ 18 F]fluoro-6-