Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

Munk, Ditte Emilie; Kirk, Frederik Teicher; Vendelbo, Mikkel Holm; Vase, Karina H.; Munk, Ole Lajord; Ott, Peter; Sandahl, Thomas Damgaard

doi:10.3791/65109

Cited by 3 publications

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“…The PET/CT procedure, image analysis, blood analysis, and radiotracer preparation have been detailed. 12 , 16 …”

Section: Methodsmentioning

confidence: 99%

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

Kirk,

Munk,

Swenson

et al. 2023

Hepatology

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Background and Aims: Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption. Approach and Results: Sixteen healthy volunteers were examined with positron emission tomography/CT 1 and 15 hours after an oral Copper-64 (64Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64Cu positron emission tomography/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64Cu uptake reflect the effect of drugs on intestinal absorption. 64Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64Cu activity 1 hour after 64Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p<0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p<0.02, indicating strong inhibition of intestinal 64Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p<0.04. Conclusions: In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.

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“…The PET/CT procedure, image analysis, blood analysis, and radiotracer preparation have been detailed. 12 , 16 …”

Section: Methodsmentioning

confidence: 99%

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

Kirk,

Munk,

Swenson

et al. 2023

Hepatology

Self Cite

View full text Add to dashboard Cite

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Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease

Kirk,

Munk,

Swenson

et al. 2024

Journal of Hepatology

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Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression

Cui,

Du,

et al. 2024

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

Cited by 3 publications

References 0 publications

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

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

Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease

Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression

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