In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis

Area of Science:

• Cardiovascular Imaging
• Molecular Imaging
• Nuclear Medicine

Background:

• Intraplaque angiogenesis and inflammation are key drivers of atherosclerosis, mediated by the alpha-V beta-3 (αvβ3) integrin pathway.
• Assessing these processes in human aortic atherosclerosis is crucial for understanding disease progression and vulnerability.

Purpose of the Study:

• To investigate the applicability of the αvβ3-integrin receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide for assessing human aortic atherosclerosis.
• To correlate 18F-fluciclatide uptake with established measures of atherosclerotic burden and disease activity.

Main Methods:

• Forty-six subjects with stable or unstable atherosclerotic disease underwent PET and CT imaging after 18F-fluciclatide administration.
• Ex vivo analysis of carotid endarterectomy samples (autoradiography, immunohistochemistry) evaluated vascular 18F-fluciclatide binding.
• In vivo kinetic modeling and static imaging quantified thoracic aortic 18F-fluciclatide uptake, correlated with CT-derived measures of atherosclerotic burden.

Main Results:

• 18F-Fluciclatide uptake co-localized with αvβ3 integrin expression, inflammation, and angiogenesis markers.
• In vivo uptake correlated significantly with aortic wall thickness (r=0.57), plaque volume (r=0.56), and calcium score (r=0.37).
• Patients with recent myocardial infarction showed greater aortic 18F-fluciclatide uptake compared to those with stable disease.

Conclusions:

• In vivo αvβ3 integrin expression in human aortic atheroma correlates with plaque burden and is elevated in patients with recent myocardial infarction.
• 18F-fluciclatide PET imaging offers a potential method for quantifying αvβ3 integrin expression.
• This technique may aid in assessing plaque vulnerability and disease activity in atherosclerosis.