18F-Fluoride Positron Emission Tomography for Identification of Ruptured and High-Risk Coronary Atherosclerotic Plaques: A Prospective Clinical Trial

Study Questions:

Can positron emission tomography (PET) imaging identify high-risk or ruptured coronary artery plaque?

Methods:

This study examined 40 patients with acute myocardial infarction (AMI) and 40 patients with stable angina undergoing invasive coronary angiography, and compared findings between 18F-NaF and 18F-FDG PET-CT. In patients with AMI, PET-CT uptake was compared between culprit plaque and the highest uptake in nonculprit vessels. In patients with stable angina, PET-CT uptake was compared to intravascular ultrasound findings between plaques with versus without significant uptake by PET-CT. In addition, nine evaluable patients undergoing carotid endarterectomy for symptomatic carotid artery disease were evaluated, and 18F-NaF PET-CT imaging was compared to plaque rupture on pathological specimens. Patients <50 years of age, insulin-dependent diabetics, and those with study contraindications were excluded.

Results:

In patients with AMI and stable angina, mean age was 62 ± 8 and 67 ± 8 years, and 93% and 90% were males, respectively. In those with AMI, the highest coronary uptake by 18F-NaF was observed in culprit lesions in 37/40 (93% of cases). The median peak ratio of tissue to background uptake was significantly different between culprit and nonculprit lesions [1.66 (interquartile range [IQR] 1.40-2.25) vs. 1.24 (IQR 1.06-1.38), p < 0.001]; in contrast, using 18F-FDG, there was no significant difference observed between culprit and nonculprit lesions [1.71 (IQR 1.40-2.13) vs. 1.58 (IQR 1.28-2.01), p = 0.34]. In patients with stable angina, focal uptake by 18F-NaF PET was noted in 18/40 patients (45%), and these lesions were associated with increased prevalence of high-risk plaque features by intravascular ultrasound (positive remodeling, micro-calcification, and necrotic core, p < 0.01 for each); in contrast, focal uptake by 18F-FDG PET was noted only in four sites of recent revascularization. Finally, on carotid imaging, focal uptake by 18F-NaF PET was noted at the site of all carotid plaque ruptures, and was associated with unstable plaque characteristics on histology.

Conclusions:

18F-NaF PET-CT represents a novel method to identify high-risk and ruptured coronary artery plaque.

Perspective:

While there are many methods to identify coronary artery disease, there are limited means at present to discriminate plaques that convey higher risk. The present findings suggest that 18F-NaF PET-CT may represent a novel noninvasive approach to identify ruptured and high-risk plaque. This study demonstrates a high rate of agreement between focal uptake and ruptured plaque in patients with AMI, and noted that lesions with focal uptake in patients with stable angina were positively associated with high-risk plaque features on intravascular ultrasound. This opens several potential fronts for further research. For example, can this technique identify patients at increased risk of adverse events? Can this be used to determine which patients and lesions may benefit from coronary revascularization? Can this method monitor changes in plaque characteristics over time? These results will undoubtedly foster many new investigations, which may significantly advance our understanding of coronary artery disease over the limited data available with current noninvasive strategies.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Computed Tomography, Nuclear Imaging, Chronic Angina

Keywords: Coronary Artery Disease, Myocardial Infarction, Fluorodeoxyglucose F18, Plaque, Atherosclerotic, Angina, Stable, Fluorides, Coronary Angiography, Endarterectomy, Carotid, Calcinosis, Carotid Artery Diseases, Positron-Emission Tomography


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