A fluorinated azine as a versatile scaffold for the development of Cu (Ⅱ)-specific multi-functional imaging probes

摘要

Copper is vital to many physiological activities, and its dyshomeostasis is related to cancers as well as neuro-degenerative 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 Cu~(2+) ion, forming a 1∶1 FN-Cu~(2+) complex, and induces a substantial fluorescence quenching, which can be resumed upon addition of H_2S (Na_2S as the source of H_2S). The binding of the paramagnetic Cu~(2+) ions also leads to the relaxation enhancement of the ~(19)F nuclei in the FN-Cu~(2+) complex and improve the signal-to-noise ratio of the phantom images. The ~(18)F-radio-labeled analogue, [~(18)F]FN, is synthesized for the first time and used in PET/CT imaging on cynomolgus for a preliminary study of pharmacokinetics.