TY - JOUR
T1 - Imaging zinc trafficking in vivo by positron emission tomography with zinc-62
AU - Firth, George
AU - Yu, Zilin
AU - Bartnicka, Joanna J
AU - Parker, David
AU - Kim, Jana
AU - Sunassee, Kavitha
AU - Greenwood, Hannah E
AU - Al-Salamee, Fahad
AU - Jauregui-Osoro, Maite
AU - Di Pietro, Alberto
AU - Guzman, Joanna
AU - Blower, Philip J
PY - 2022/10/6
Y1 - 2022/10/6
N2 - Abstract 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 PET imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via 62Cu (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/62Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. Methods 62 Zn prepared by proton irradiation of natural copper foil was used to construct a conventional 62 Zn/62Cu generator. 62 Zn was eluted using trisodium citrate and used for biological experiments, compared with 64Cu in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. Results [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 [64Cu]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post injection). Between 4 h and 24 h, 62 Zn retention in liver, pancreas and kidney declined over time, while brain uptake increased. Like 64Cu, 62 Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Conclusions Although it offers limited reliability of scanning before one hour post-injection, 62Zn-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.
AB - Abstract 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 PET imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via 62Cu (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/62Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. Methods 62 Zn prepared by proton irradiation of natural copper foil was used to construct a conventional 62 Zn/62Cu generator. 62 Zn was eluted using trisodium citrate and used for biological experiments, compared with 64Cu in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. Results [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 [64Cu]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post injection). Between 4 h and 24 h, 62 Zn retention in liver, pancreas and kidney declined over time, while brain uptake increased. Like 64Cu, 62 Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Conclusions Although it offers limited reliability of scanning before one hour post-injection, 62Zn-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.
KW - Metals and Alloys
KW - Biochemistry
KW - Biomaterials
KW - Biophysics
KW - Chemistry (miscellaneous)
U2 - 10.1093/mtomcs/mfac076
DO - 10.1093/mtomcs/mfac076
M3 - Article
SN - 1756-5901
VL - 14
JO - Metallomics
JF - Metallomics
IS - 10
M1 - mfac076
ER -