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

Study Questions:

What is the ability of combined positron emission tomography (PET) and computed tomography (CT) using 18F-sodium fluoride (18F-NaF) uptake to identify ruptured and high-risk atherosclerotic plaques in patients with symptomatic coronary and carotid artery disease?

Methods:

In this prospective clinical trial, patients with myocardial infarction (n = 40) and stable angina (n = 40) underwent 18F-NaF and 18F-fluorodeoxyglucose (18F-FDG) PET-CT, and invasive coronary angiography.18F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of 18F-fluoride tissue-to-background ratios of culprit and nonculprit coronary plaques of patients with acute myocardial infarction.

Results:

In 37 (93%) patients with myocardial infarction, the highest coronary 18F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1.66 [interquartile range (IQR) 1.40–2.25] vs. highest nonculprit 1.24 [1.06–1.38], p < 0.0001). By contrast, coronary 18F-FDG uptake was commonly obscured by myocardial uptake, and where discernible, there were no differences between culprit and nonculprit plaques (1.71 [1.40–2.13] vs. 1.58 [1.28–2.01], p = 0.34). Marked 18F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. Eighteen (45%) patients with stable angina had plaques with focal 18F-NaF uptake (maximum tissue-to-background ratio 1.90 [IQR, 1.1–2.17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodeling (remodeling index 1.12 [1.09–1.19] vs. 1.01 [0.94–1.06]; p = 0.0004), microcalcification (73% vs. 21%, p = 0.002), and necrotic core (25% [21–29] vs. 18% [14–22], p = 0.001).

Conclusions:

The authors concluded that 18F-NaF PET-CT is the first noninvasive imaging method to identify and localize ruptured and high-risk coronary plaque.

Perspective:

This study reported that intense 18F-NaF uptake localizes to recent plaque rupture in patients with acute myocardial infarction and in those with symptomatic carotid disease. Furthermore, in patients with stable coronary artery disease, 18F-NaF uptake seems to identify coronary plaques with high-risk features on intravascular ultrasound. While this technique holds major promise as a means of identifying high-risk and ruptured plaque, additional research is indicated to determine whether 18F-fluoride PET will provide a means of improving risk stratification, guiding therapeutic interventions, and assessing novel antiatherosclerotic therapies to make actual and meaningful improvement in clinical outcomes.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Novel Agents, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Endarterectomy, Coronary Artery Disease, Myocardial Infarction, Apoptosis, Plaque, Atherosclerotic, Calcinosis, Carotid Artery Diseases, Positron-Emission Tomography, Fluorodeoxyglucose F18, Coronary Angiography, Tomography, Cardiology, Cardiovascular Diseases, Radiopharmaceuticals, Sodium Fluoride, Necrosis


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