TY - JOUR
T1 - The pathophysiology of Wilson’s disease visualized
T2 - A human
64Cu PET study
AU - Sandahl, Thomas Damgaard
AU - Gormsen, Lars Christian
AU - Kjærgaard, Kristoffer
AU - Vendelbo, Mikkel
AU - Munk, Ditte Emilie
AU - Munk, Ole Lajord
AU - Bender, Dirk
AU - Keiding, Susanne
AU - Vase, Karina Højrup
AU - Frisch, Kim
AU - Vilstrup, Hendrik V Arenstorff
AU - Ott, Peter
PY - 2022/6
Y1 - 2022/6
N2 - Background and Aims Wilson's 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 PET with copper-64 (Cu-64) as a tracer. Furthermore, we assessed the diagnostic potential of the method. Approach and Results Nine patients with WD, 5 healthy heterozygote subjects, and 8 healthy controls were injected with an i.v. bolus of Cu-64 followed by a 90-min dynamic PET scan of the liver and static whole-body PET/CT scans after 1.5, 6, and 20 h. Blood Cu-64 concentrations were measured in parallel. Hepatic copper retention and redistribution were evaluated by standardized uptake values (SUVs). At 90 min, hepatic SUVs were similar in the three groups. In contrast, at 20 h postinjection, the SUV in WD patients (mean +/- SEM, 31 +/- 4) was higher than in heterozygotes (24 +/- 3) and controls (21 +/- 4; p < 0.001). An SUV-ratio of hepatic Cu-64 concentration at 20 and 1.5 h completely discriminated between 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 Cu-64 was estimated to be slightly lower in patients with WD than in controls (p = 0.04). Conclusions Cu-64 PET imaging enables visualization and quantification of the hepatic copper retention characteristic for WD patients. This method represents a valuable tool for future studies of WD pathophysiology, and may assist the development of therapies, and accurate diagnosis.
AB - Background and Aims Wilson's 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 PET with copper-64 (Cu-64) as a tracer. Furthermore, we assessed the diagnostic potential of the method. Approach and Results Nine patients with WD, 5 healthy heterozygote subjects, and 8 healthy controls were injected with an i.v. bolus of Cu-64 followed by a 90-min dynamic PET scan of the liver and static whole-body PET/CT scans after 1.5, 6, and 20 h. Blood Cu-64 concentrations were measured in parallel. Hepatic copper retention and redistribution were evaluated by standardized uptake values (SUVs). At 90 min, hepatic SUVs were similar in the three groups. In contrast, at 20 h postinjection, the SUV in WD patients (mean +/- SEM, 31 +/- 4) was higher than in heterozygotes (24 +/- 3) and controls (21 +/- 4; p < 0.001). An SUV-ratio of hepatic Cu-64 concentration at 20 and 1.5 h completely discriminated between 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 Cu-64 was estimated to be slightly lower in patients with WD than in controls (p = 0.04). Conclusions Cu-64 PET imaging enables visualization and quantification of the hepatic copper retention characteristic for WD patients. This method represents a valuable tool for future studies of WD pathophysiology, and may assist the development of therapies, and accurate diagnosis.
KW - (CUCL2)-CU-64 PET/CT
KW - COPPER-METABOLISM
KW - DIAGNOSIS
KW - EXPERIENCE
KW - LIVER
KW - MOUSE MODEL
KW - RADIOCOPPER
KW - Hepatolenticular Degeneration/diagnostic imaging
KW - Positron Emission Tomography Computed Tomography
KW - Humans
KW - Heterozygote
KW - Positron-Emission Tomography
U2 - 10.1002/hep.32238
DO - 10.1002/hep.32238
M3 - Journal article
C2 - 34773664
SN - 0270-9139
VL - 75
SP - 1461
EP - 1470
JO - Hepatology
JF - Hepatology
IS - 6
ER -