A novel versatile precursor suitable for ¹⁸ F-radiolabeling via "click chemistry"

As an effort to improve ¹⁸ F-radiolabeling of biomolecules in method robustness and versatility, we report the synthesis and radiolabeling of a new azido precursor potentially useful for the so-called "click reaction," in particular the ligand-free version of the copper(I)-catalyzed alkyne-azide cycloaddition. The new azido precursor may help to overcome problems sometimes exhibited by most of the currently used analogues, as it is safe to handle and it displays long-term chemical stability, thus facilitating the development of new radiolabeling procedures. Moreover, the formed ¹⁸ F-labeled 1,2,3-triazole is potentially metabolically stable and could enhance the in vivo circulation time. The above azido precursor was successfully radiolabeled with ¹⁸ F, with 51% radiochemical yield (nondecay-corrected). As a proof of concept, the ¹⁸ F-labeled azide was then tested with a suitable alkyne functionalized aminoacid (l-propargylglycine), showing 94% of conversion, and a final radiochemical yield of 27% (>99% radiochemical purity), nondecay-corrected, with a total preparation time of 104 minutes.