Imaging Carotid Artery Atherosclerosis with Positron Emission Tomography: Applications, Radioligands, and Limitations

Introduction: 1. Investigate the utility of PET radiotracers in the early detection and characterization of carotid artery atherosclerosis 2. Identify areas for future research and development in this field.

Methods: PubMed, Web of Science, Scopus, and Google Scholar, were utilized to conduct a thorough and comprehensive review of the literature. The search included meta-analyses, abstracts, and original research (prospective and retrospective studies). Data on study design, sample size, radioligands used, conclusions drawn, and limitations were extracted from each study. The gathered information was synthesized to provide an overview of current understanding on the use of PET for early detection and treatment monitoring of atherosclerosis.

Results: Carotid Artery atherosclerosis is a common form of arterial disease in which plaque builds up on the inner walls of the carotid arteries, which are the major blood vessels that supply oxygenated blood to the head and neck. Plaque accumulation can narrow the arteries and decrease blood flow to the brain. This can increase the risk of stroke and transient ischemic attack (TIA). A number of research studies have explored the use of various PET tracers for the imaging of different aspects of atherosclerosis. Two commonly used radiotracers in the imaging of atherosclerosis are ¹⁸F-sodium fluoride (NaF) and ¹⁸F-fluorodeoxyglucose (FDG). NaF and FDG have different correlations with microcalcification in histological studies, which can be a reflection of the fact that FDG is more suited for identifying inflammation during the development of atherosclerosis while NaF is more suitable for the assessment of long-term complications. NaF is significantly associated with the severity of ischemic vascular brain disease as observed on MRI.

FDG-PET/CT has been used to measure inflammation by measuring macrophage density, while NaF-PET/CT can determine the extent of ongoing microcalcification. NaF has been found to be more sensitive than other PET tracers in this regard. FMISO-PET demonstrates an ability to identify hypoxia, while RGD-PET (which targets αvβ3 integrin) can detect neoangiogenesis. 68Ga-Pentixafor-PET can quantify the levels of the inflammatory marker CXCR4, a type 4 chemokine receptor. This technique has the potential to serve as a surrogate marker for inflammatory atherosclerosis. Overall, these PET tracers have shown promise in providing valuable information about the progression and treatment of atherosclerosis. Studies that have utilized FDG-PET and CT angiography (CTA) to image the carotid arteries of patients who had experienced an ischemic stroke report that the carotid artery ipsilateral to the stroke displayed higher FDG uptake and a higher prevalence of high-risk plaque features, such as hypodense plaques and extensive hypodensity, compared to the contralateral artery. This implies that non-stenotic plaques with high FDG uptake may play a causal role in ischemic stroke. While these multimodal approaches demonstrate evidence for the use of PET/CT in the diagnosis of carotid artery atherosclerosis, there is a scarcity of research on the associated risk factors.

Conclusions: PET imaging has shown promise in the diagnosis and evaluation of carotid artery atherosclerosis, a common and potentially serious form of arterial disease. The use of various PET tracers can provide valuable information about different aspects of the disease. Specific tracers, such as NaF, provide useful information regarding the extent and severity of carotid artery disease. Future studies should explore the use of different PET tracers and multimodal imaging approaches to improve the accuracy and sensitivity of diagnosis; in order to provide prognostic value, further prospective research investigating the ability of PET imaging to predict long-term prognosis is required.