Targeted molecular CT imaging of atherosclerosis and abdominal aortic aneurysm

Atherosclerosis and abdominal aortic aneurysm (AAA) share the same pathological triad, which includes chronic inflammation, immune cell infiltration, and extracellular matrix (ECM) degradation. Both diseases are characterized by the fact that the disease process may not be diagnosed until a life-threatening event occurs. Current imaging methods diagnose these conditions by assessing the degree of stenosis of the blood vessel, the plaque burden, and the aneurysm diameter. Unfortunately, these methods are not sufficient to measure biological activity, which is important to determine if such potentially life-threatening events will occur and where they will occur. Molecular imaging, together with computed tomography (CT), might close this gap. CT offers several benefits: it is widely available, allows rapid acquisition, can be integrated into vascular workflows, and can provide quantitative signal readout, but its main use has been in the context of anatomical detail. Recent preclinical studies suggest that a shift may be occurring in this area. This review examines the use of molecular CT imaging for the diagnosis of atherosclerosis and AAA, systematically grouped by molecular target. There are three different approaches that are employed in the current literature. The most clinically advanced is the first, macrophage-targeted probes. The second, high-density lipoprotein (HDL)-mimetic nanoparticles, takes advantage of an endogenous lipoprotein pathway, but not an engineered ligand. The third, gold nanoparticles, which targeted elastin, yielded the most clinically relevant finding to date: ex vivo signal correlates inversely with aortic wall burst pressure, casting doubt on whether diameter is sufficient to assess for rupture. Comparable methods for targeting biomarkers with CT have not been developed, although magnetic resonance imaging (MRI) and nuclear imaging modalities can already target matrix metalloproteinase (MMP) activity, vascular cell adhesion molecule-1 (VCAM-1), and microcalcification. This is a space that could be very fruitful for future studies.