Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs

Area of Science:

• Molecular imaging
• Cardiovascular research
• Biomedical engineering

Background:

• Receptor for advanced glycated end product (RAGE) expression is a key feature of atherosclerosis.
• Previous studies in mice demonstrated radiolabeled anti-RAGE antibody uptake in atherosclerotic plaques.

Purpose of the Study:

• To evaluate RAGE-directed imaging for identifying advanced atherosclerotic plaques in a large animal model.
• To assess the potential of anti-RAGE antibodies as diagnostic and therapeutic agents.

Main Methods:

• Hyperlipidemic pigs received technetium-99m-labeled anti-RAGE F(ab')2 antibody injection.
• Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed after 6 hours.
• Arterial segments were dissected, stained for RAGE, and classified using AHA criteria post-imaging.

Main Results:

• SPECT/CT imaging revealed focal vascular uptake corresponding to advanced atherosclerotic lesions (AHA class III/IV) in coronary and carotid arteries.
• Significant correlation was observed between tracer uptake (%ID/g) and RAGE staining intensity.
• Uptake was also noted in hind limb small arteries of hyperlipidemic pigs, correlating with RAGE staining.

Conclusions:

• Radiolabeled anti-RAGE antibody uptake in advanced plaques and small arteries validates RAGE's role in atherosclerosis and peripheral artery disease.
• RAGE-directed imaging shows promise for identifying advanced atherosclerotic lesions in a relevant large animal model.
• This supports RAGE as a potential target for both imaging and therapeutic interventions in cardiovascular diseases.