Visualizing hepatic copper release in Long-Evans cinnamon rats using single-photon emission computed tomography

Area of Science:

• Biomedical Imaging
• Radiochemistry
• Molecular Biology

Background:

• Wilson's disease is a genetic disorder characterized by excessive copper accumulation in the liver.
• Accurate detection of hepatic copper is crucial for diagnosis and monitoring of Wilson's disease.
• Existing imaging techniques may have limitations in sensitivity or specificity for hepatic copper.

Purpose of the Study:

• To investigate the utility of a novel prion-derived peptide imaging agent labeled with indium-111 for detecting hepatic copper.
• To evaluate the agent's performance in a Long-Evans Cinnamon (LEC) rat model of Wilson's disease.
• To compare the SPECT imaging results with a control agent lacking the copper-binding moiety.

Main Methods:

• Solid-phase peptide synthesis was used to create an imaging agent with a prion protein-derived copper-binding moiety and an indium-111 radiolabel.
• The indium-labeled agent and a control agent were administered intravenously to LEC rats and healthy Long-Evans (LE) rats.
• Pharmacokinetics were assessed using single-photon emission computed tomography (SPECT) over one hour, followed by liver necropsy.

Main Results:

• LEC rats showed approximately double the hepatic radioactivity compared to healthy LE rats when injected with the indium-labeled agent.
• The control agent, lacking the copper-binding moiety, exhibited similar hepatic signals in both rat groups, indicating specificity.
• In vivo copper exposure in mice altered the agent's pharmacokinetics, confirming its sensitivity to extracellular copper levels.

Conclusions:

• The developed indium-labeled prion-based imaging agent demonstrates significant potential for detecting hepatic copper accumulation in Wilson's disease.
• SPECT imaging with this agent offers improved detection capabilities compared to previous MRI applications.
• This agent represents a promising tool for non-invasive assessment of copper burden in liver disease models.