Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study

Abstract

Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson’s disease (WD). We used copper-64 (64Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic 64Cu content after oral 64Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic 64Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered 64Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients.

Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans

“…This approach has been previously detailed and eliminates signal spillout from other organs such as the colon, large blood vessels within the liver, and the effect of respiratory motion. [15] Three VOIs were placed in the luminal center of the transverse colon, each 0.5 mL in volume. Due to the temporospatial movement of intestinal contents, colonic 64 Cu activity at 1H was likely zero, and any present signal likely spilled out from nearby segments of the small intestines.…”

“…This method was previously used to estimate the similar effects of zinc. [15] The activity was expressed as mean standard uptake value (SUV) which is the mean activity per mL organ normalized to a dose of 64 Cu and body weight after correction for radioactivity decay:…”

“…The inhibition of intestinal uptake was estimated as the posttreatment hepatic SUV reduction at the scan 1H or 15H after the oral 64 Cu dose as has been detailed. [15] Secondary endpoints included the 64 Cu activity in venous samples and other organs of interest including the colon, kidney, and bladder. Venous 64 Cu levels, given as kBq/mL were corrected for decay, body weight, and ingested dose.…”

“…[12][13][14] We have previously shown that a dose of orally administered 64 Cu can be followed by 64 Cu PET/CT showing quantitative hepatic uptake and subsequent biliary excretion. [12,15] We have also demonstrated how the effect of zinc on intestinal copper uptake could be quantified using PET/CT to measure how the treatment reduced hepatic 64 Cu levels after an oral dose of 64 Cu. [15] The present study aimed to examine and quantify the potential inhibition of intestinal copper uptake by TRI and PEN using 64 Cu PET/CT.…”

“…[12,15] We have also demonstrated how the effect of zinc on intestinal copper uptake could be quantified using PET/CT to measure how the treatment reduced hepatic 64 Cu levels after an oral dose of 64 Cu. [15] The present study aimed to examine and quantify the potential inhibition of intestinal copper uptake by TRI and PEN using 64 Cu PET/CT. The measurements were performed before and after 7 days of treatment with either PEN or TRI.…”