From incidental positron emission uptake to in-vivo phenotyping: a short history of positron emission tomography in the study of atherosclerosis and the vulnerable plaque

Positron emission tomography (PET) imaging has evolved over the last 20 years to a powerful tool for assessing vascular biology. The incidental uptake of PET tracers to the vessel wall provided the substrate for creating dedicated protocols and introducing novel agents for molecular imaging that targeted specific pathobiological mechanisms involved in the atherosclerotic process. Preliminary work with 18 F-FDG underscored its efficacy to detect macrophage-rich inflammation, while, subsequent studies using 18 F-NaF demonstrated its ability to detect active microcalcification and high-risk plaques. These encouraging results lead to the development of a new generation of tracers targeting macrophage receptors, chemokine signalling, angiogenesis, endothelial activation, and mitochondrial activity that have been validated against histology in animal models, endarterectomy, and autopsy tissue. This review provides an overview in the field describing the evolution of PET imaging in the study of atherosclerosis. It summarises the existing and emerging tracers, presents the biological processes that have been targeted by PET agents and collates the evidence from studies for vulnerable-plaque detection. Finally, it outlines technical hurdles and the current limitations of PET imaging that need to be addressed for clinical translation.