Introduction18F-sodium fluoride (NaF) positron-emission tomography (PET) is increasingly being used to measure microcalcification in atherosclerotic diseasein vivo. Correlations have been drawn between sodium fluoride uptake and the presence of high-risk plaque features, as well as its association with clinical atherosclerotic sequelae. The aim of this review was to perform a meta-analysis of NaF uptake on PET imaging and its relation to symptomatic and asymptomatic disease.MethodsA systematic review was performed according to PRISMA guidelines, via searching the MEDLINE database up to August 2023. The search strategy included the terms “NaF”, “PET” and “plaque”, and all studies were included where there was data listed regarding the degree of microcalcification, as measured by18F-NaF uptake in symptomatic and asymptomatic atherosclerotic plaques. Analysis involved calculating standardized mean differences between uptake values and comparison using a random-effects model.ResultsA total of 15 articles, involving 423 participants, were included in the meta-analysis. Comparing18F-NaF uptake in symptomatic vs asymptomatic atherosclerotic plaques, a standardized mean difference of 0.42 (95% CI 0.29-0.56; p<0.001, I2= 54.1%) was noted for those studies comparing symptomatic and asymptomatic plaques in the same participant, with no significant change in effect based on arterial territory studied (QM= 5.02, p = 0.08). In those studies where data was included from participants with and without symptomatic disease, the standardized mean difference between symptomatic and asymptomatic plaques was 0.44 (95% CI 0.03-0.85, p=0.037, I2= 40.4%). All studies including asymptomatic participants were investigating carotid disease.ConclusionsPET imaging using18F-NaF can detect differences in microcalcification between symptomatic and asymptomatic atherosclerotic plaques within and between individuals, and is a marker of symptomatic disease. The standardization of18F-NaF PET imaging protocols, and its future use as a risk stratification tool or outcome measure, requires further study.