Imaging zinc trafficking in vivo by positron emission tomography with zinc-62

Non-invasive imaging techniques to dynamically map whole-body trafficking of essential metals in vivo in health and diseases are needed. Despite (62)Zn having appropriate physical properties for positron emission tomography (PET) imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via (62)Cu (half-life, 10 min; positron emission, 97%) has limited its use. We aimed to develop a method to extract (62)Zn from a (62)Zn/(62)Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. (62)Zn prepared by proton irradiation of natural copper foil was used to construct a conventional (62)Zn/(62)Cu generator. (62)Zn was eluted using trisodium citrate and used for biological experiments, compared with (64)Cu in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. [(62)Zn]Zn-citrate was readily eluted from the generator with citrate buffer. PET imaging with the eluate demonstrated biodistribution similar to previous observations with the shorter-lived (63)Zn (half-life 38.5 min), with significant differences compared to [(64)Cu]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post-injection). Between 4 and 24 h, (62)Zn retention in liver, pancreas, and kidney declined over time, while brain uptake increased. Like (64)Cu, (62)Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Although it offers limited reliability of scanning before 1 h post-injection, (62)Zn-PET allows investigation of zinc trafficking in vivo for >24 h and hence provides a useful new tool to investigate diseases where zinc homeostasis is disrupted in preclinical models and humans.