Abstract
Acute coronary syndrome (ACS) describes a range of conditions associated with the rupture of high-risk or vulnerable plaque. Vulnerable atherosclerotic plaque is associated with many changes in its microenvironment which could potentially cause rapid plaque progression. Present-day PET imaging presents a plethora of radiopharmaceuticals designed to image different characteristics throughout plaque progression. Improved knowledge of atherosclerotic disease pathways has facilitated a growing number of pathophysiological targets for more innovative radiotracer design aimed at identifying at-risk vulnerable plaque and earlier intervention opportunity. This paper reviews the efficacy of PET imaging radiotracers 18F-FDG, 18F-NaF, 68Ga-DOTATATE, 64Cu-DOTATATE and 68Ga-pentixafor in plaque characterisation and risk assessment, as well as the translational potential of novel radiotracers in animal studies. Finally, we discuss our murine PET imaging experience and the challenges encountered.
Highlights
The goal of non-invasive imaging of atherosclerotic plaques is to enable better prediction of cardiovascular (CV) events by improving assessment of asymptomatic, at-risk plaque
In rabbits, 125 I-pentixafor accumulated in inflamed plaques, which was verified histologically by the detection of macrophages and CXCR4 in plaques of the abdominal aorta and carotid artery [60]. These findings present a complex system of CXCR4-expressing cell types that, depending on the activating ligand, may have athero-protective or atherogenic effects
Uptake of 89 Zr-Mal-HAS in atherosclerotic lesions of ApoE-/- mice was higher compared to 18 F-FDG, and the difference compared to wild-type mice indicates increased specificity for macrophage-targeted imaging, especially in early atherosclerosis [87]
Summary
The goal of non-invasive imaging of atherosclerotic plaques is to enable better prediction of cardiovascular (CV) events by improving assessment of asymptomatic, at-risk plaque. FDG is a glucose analogue and the most-validated radiotracer for imaging high metabolically active inflammatory cells (e.g., macrophages) and tissues (e.g., atherosclerotic plaques) in animal models and humans [10]. M1 macrophages are pro-inflammatory and more glycolytically active than M2 antiinflammatory cells [12] Another concerning factor that can affect imaging results and outcome is the non-specific uptake by highly glycolytic cells in the arterial wall [13]. The metabolic profiles generated comparable levels of glucose uptake in cultured macrophages and murine atherosclerotic plaques These findings suggest that FDG uptake is an indicator of vascular macrophage burden and numbers, it may not necessarily differentiate morphologically unstable from stable plaque, or identify those at risk of rupture and symptomatic atherothrombosis [15]. This becomes of concern in the coronary arteries, where spillover from the physiologic activity of the heart obscures detection and accurate quantification of FDG uptake and plaque inflammation [19]
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