The pathophysiology of Wilson’s disease visualized: A human 64Cu PET study

Autor: Ditte Emilie Munk, Lars C. Gormsen, Susanne Keiding, Ole Lajord Munk, Karina H. Vase, Hendrik Vilstrup, Thomas Damgaard Sandahl, Kim Frisch, Peter Ott, Dirk Bender, Mikkel H. Vendelbo, Kristoffer Kjærgaard
Rok vydání: 2022
Předmět:
Zdroj: Sandahl, T D, Gormsen, L C, Kjaergaard, K, Vendelbo, M H, Munk, D E, Munk, O L, Bender, D, Keiding, S, Vase, K H, Frisch, K, Vilstrup, H & Ott, P 2021, ' The pathophysiology of Wilson disease visualised : A human 64 Cu PET study ', Hepatology . https://doi.org/10.1002/hep.32238
Sandahl, T D, Gormsen, L C, Kjærgaard, K, Vendelbo, M, Munk, D E, Munk, O L, Bender, D, Keiding, S, Vase, K H, Frisch, K, Vilstrup, H V A & Ott, P 2022, ' The pathophysiology of Wilson’s disease visualized : A human 64 Cu PET study ', Hepatology, vol. 75, no. 6, pp. 1461-1470 . https://doi.org/10.1002/hep.32238
ISSN: 1527-3350
0270-9139
DOI: 10.1002/hep.32238
Popis: BACKGROUND & AIMS: Wilson disease (WD) is a genetic disease with systemic accumulation of copper that leads to symptoms from the liver and brain. However, the underlying defects in copper transport kinetics are only partly understood. We sought to quantify hepatic copper turnover in patients with WD compared with heterozygote and control subjects using positron emission tomography (PET) with copper-64 (64 Cu) as tracer. Furthermore, we assessed the diagnostic potential of the method.METHODS: Nine patients with WD, five healthy heterozygote subjects, and eight healthy controls were injected with an intravenous bolus of 64 Cu followed by a 90-min dynamic PET scan of the liver and static whole-body PET/CT scans after 1.5, 6, and 20 hours. Blood 64 Cu concentrations were measured in parallel. The hepatic copper retention and redistribution were evaluated by standardized uptake values (SUV).RESULTS: At 90 min, the hepatic SUVs were similar in the three groups. In contrast, at 20 hours post injection, the SUV in WD patient (Mean±SEM 31±4) was higher than in heterozygotes (24±3) or controls (21±4), (p < 0.001). An SUV-ratio of the hepatic 64 Cu concentration at 20 and 1.5 hours completely discriminated between the WD patients and control groups (p < 0.0001; ANOVA). By Patlak-analysis of the initial 90 min of the PET scan, the steady-state hepatic clearance of 64 Cu was estimated to be slightly lower in the patients with WD than in controls, (p = 0.04).CONCLUSIONS: 64 Cu PET imaging enables visualisation and quantification of the hepatic copper retention characteristic for WD patients. This method represents a valuable tool for future studies of WD pathophysiology, which may assist the development of novel therapies, and accurate diagnosis.
Databáze: OpenAIRE
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