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 Zn-62 having appropriate physical properties for positron emission tomography (PET) imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via Cu-62 (half-life, 10 min; positron emission, 97%) has limited its use. We aimed to develop a method to extract Zn-62 from a Zn-62/Cu-62 generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. Zn-62 prepared by proton irradiation of natural copper foil was used to construct a conventional Zn-62/Cu-62 generator. Zn-62 was eluted using trisodium citrate and used for biological experiments, compared with Cu-64 in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. [Zn-62]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 Zn-63 (half-life 38.5 min), with significant differences compared to [Cu-64]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post-injection). Between 4 and 24 h, Zn-62 retention in liver, pancreas, and kidney declined over time, while brain uptake increased. Like Cu-64, Zn-62 showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Although it offers limited reliability of scanning before 1 h post-injection, Zn-62-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.