Click labeling with 2-[18F]fluoroethylazide for positron emission tomography

As an effort in the development of more flexible F-18-labeling chemistry, we report herein on the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as the "click reaction", to form F-18-labeled 1,2,3-triazoles. Nucleophilic fluorination of 2-azidoethyl-4-toluenesulfonate followed by distillation provided 2-[F-18]fluoroethylazide in 55% radiochemical yield (decay-corrected). 2-[F-18]fluoroethylazide was reacted with a small library of terminal alkynes in the presence of excess Cu2+/ascorbate or copper powder. The most reactive alkyne, N-benzylpropynamide provided nearly quantitative incorporation of 2-[F-18]fluoroethylazide after 15 min at ambient temperature, whereas the majority of the alkyne substrates provided excellent yields of the corresponding F-18-labeled 1,2,3-triazoles following heating to 80 degrees C. Using the method described, a model peptide was obtained in 92.3 +/- 0.3% (n = 3) radiochemical yield (decay-corrected) after purification by semipreparative HPLC.