New strategy for the preparation of clickable peptides and labeling with 1-(azidomethyl)-4-[(18)F]-fluorobenzene for PET.

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides has been developed and has also permitted the straightforward preparation of reference compounds. A complementary azide labeling agent (1-(azidomethyl)-4-[(18)F]-fluorobenzene) has been produced in a four step procedure in 75 min with a 34% radiochemical yield (decay corrected). Conjugation of [(18)F]fluoroazide with a model alkyne-neuropeptide produced the desired (18)F-radiolabeled peptide in less than 15 min with a yield of 90% and excellent radiochemical purity.