Selective accumulation of [6²Zn]-labeled glycoconjugated porphyrins as multi-functional positron emission tomography tracers in cancer cells.

Positron-emission tomography (PET) can be used to visualize active stage cancer. Fluorine-18 ([(18)F])-labeled 2-([(18)F])2-deoxy-2-fluoroglucose (([(18)F])-FDG), which accumulates in glucose-dependent tissues, is a good cancer-targeting tracer. However, ([(18)F])-FDG is obscured in glucose-dependent normal tissues. In this study, we assessed the cancer-selective accumulation of zinc-labeled glycoconjugated 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (ZnGlc1-4), both in vitro and in vivo. Experiments using both normal and cancer cells confirmed the relationship between cancer cell-selective accumulation and the substitution numbers and orientations of glycoconjugated porphyrins. ZnGlctrans-2 accumulated at greater levels in cancer cells compared with other glycoconjugated porphyrins. PET imaging showed that ZnGlctrans-2 accumulated in tumor.

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 62Zn having appropriate physical properties for positron emission tomography (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 62Zn from a 62Zn/62Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. 62Zn prepared by proton irradiation of natural copper foil was used to construct a conventional 62Zn/62Cu generator. 62Zn 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. [62Zn]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 63Zn (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 and 24 h, 62Zn retention in liver, pancreas, and kidney declined over time, while brain uptake increased. Like 64Cu, 62Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Although it offers limited reliability of scanning before 1 h 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.

Performance of a 6²Zn/6²Cu microgenerator in kit-based synthesis and delivery of [6²Cu]Cu-ETS for PET perfusion imaging.

The performance of a commercially produced (62)Zn/(62)Cu microgenerator system, and an associated kit-based radiopharmaceutical synthesis method, was evaluated for clinical site production of [(62)Cu]Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion imaging. Using 37 generators, containing 1.84±0.23 GBq (62)Zn at 9:00 AM on the day of clinical use, a total of 45 patient doses of [(62)Cu]Cu-ETS (672±172 MBq) were delivered without difficulty. (62)Cu elution yields were high (approximately 90%), accompanied by extremely low (62)Zn breakthrough (<0.001%). Radiopharmaceutical preparation, from the start-of-elution to time-of-injection, consumed less than five minutes. The (62)Zn/(62)Cu microgenerator was a dependable source of short-lived positron-emitting (62)Cu, and the kit-based synthesis proved to be rapid, robust, and highly reliable for "on-demand" delivery of [(62)Cu]Cu-ETS for PET perfusion imaging.