RESUMEN
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.
Asunto(s)
Tiosemicarbazonas , Radioisótopos de Zinc , Animales , Citratos , Cobre , Radioisótopos de Cobre , Humanos , Ratones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones/métodos , Protones , Reproducibilidad de los Resultados , Distribución Tisular , Tomografía Computarizada por Rayos X , ZincRESUMEN
BACKGROUND: Over the last half-century, different stoichiometric equations for calculating the energy cost of exercise based upon the combustion of mixtures of carbohydrates, fats, and proteins have been proposed and modified. With the means of indirect calorimetry, while measuring oxygen uptake, carbon dioxide production, and urinary urea nitrogen excretion, the contribution of specific substrates to overall energy production can be estimated. However, even with their long history of application, no previous studies have evaluated whether the use of different stoichiometric equations provides similar or distinct maximal fat oxidation rate (MFO) responses and information regarding MFO location (FAT