A Fluorinated Azine As a Versatile Scaffold for the Development of Cu(II)-specific Multi-Functional Imaging Probes

Copper is vital to many physiological activities, and its dyshomeostasis is related to cancers as well as neurodegenerative diseases. Copper targeting probes with single imaging modality have been extensively reported and employed in specific aspects. Herein, we delineate the development of Cu(II)-specific multi-functional imaging probes based on a fluorinated azine FN. The azine selectively binds to a Cu2+ ion, forming a 1:1 FN-Cu2+ complex, and induces a substantial fluorescence quenching, which can be resumed upon addition of H2S (Na2S as the source of H2S). The binding of the paramagnetic Cu2+ ions also leads to the relaxation enhancement of the 19F nuclei in the FN-Cu2+ complex and improve the signal-to-noise ratio of the phantom images. The 18F-radiolabeled analogue, [18F]FN, is synthesized for the first time and used in PET/CT imaging on cynomolgus for a preliminary study of pharmacokinetics.