The methodology is described in detail in the online supplementary data. Kinetic analysis was performed on the dynamic PET studies to investigate the pharmacodynamics of 18F-fluciclatide uptake within atheroma. This study was conducted in accordance with the Declaration of Helsinki and with written informed consent of each participant. All 46 subjects underwent 18F-fluciclatide PET imaging alongside clinical assessment that included evaluation of cardiovascular risk and high-sensitivity C-reactive protein (hs-CRP) measurement (Biocheck, Foster City, California, USA). Exclusion criteria were age <40 years, women of childbearing potential, severe renal failure (estimated glomerular filtration rate <30 mL/min) or hepatic failure (Child-Pugh grade B or C), atrial fibrillation, known contrast allergy, inability to undergo scanning and inability to provide informed consent. This cohort comprised 19 unstable patients with a recent acute ST-segment elevation myocardial infarction (MI) (14☗ days after MI) ( NCT01813045), 17 and 27 stable patients with either stable angina (n=6) or asymptomatic atherosclerotic disease (n=21 12 had calcific aortic valve disease) ( NCT01837160). For in vivo imaging, 46 patients were recruited from the Royal Infirmary of Edinburgh between July 2013 and December 2014. In these patients, excised carotid plaques were examined using histology and 18F-fluciclatide autoradiography. Four patients were recruited who had sustained a recent stroke and were undergoing carotid endarterectomy. In this study, we sought to characterise the cellular and imaging characteristics of 18F-fluciclatide uptake in human atherosclerosis using a clinical cohort of patients with both stable and unstable clinical disease. 10 15 16 We hypothesised that 18F-fluciclatide may act as an imaging marker of atherosclerotic disease activity in vivo, informing about both inflammation and angiogenesis. 7ġ8F-Fluciclatide is a novel RGD-based PET radiotracer with high affinity for the α vβ 3 integrin receptor. 9 10 These tracers have also shown promise in monitoring atherosclerotic activity in preclinical models 8 11–14 and in a recent small study of patients with carotid atheroma. On this basis, several PET tracers targeting the RGD sequence have been developed for monitoring angiogenesis in malignant tumours. This receptor helps coordinate interaction between cellular components and the extracellular matrix, and contains a distinctive RGD-amino acid sequence (the arginine-glycine-aspartate motif) in the cell-ligand interaction site. 8 The integrin alpha-V beta-3 (α vβ 3) cell surface receptor is upregulated on endothelial cells in states of angiogenesis and is also observed on macrophages at sites of increased vascular inflammation, another key contributor to plaque instability. 4–7 Recently, intraplaque angiogenesis and neovascularisation has emerged as a key factor in the development, progression and instability of atherosclerotic plaques. This technique has been used to quantify vascular inflammation and calcification activity with success in both carotid and coronary atherosclerosis. 2 3Ĭombined positron emission tomography (PET) and CT is a non-invasive hybrid imaging technique that integrates targeted functional molecular imaging with high-detail anatomical definition. There is therefore considerable interest in non-invasive imaging techniques that go beyond the detection of luminal stenoses and instead focus on measuring disease activity within the vasculature. 1 Although our understanding of the pathogenesis underlying atherosclerosis has progressed over the last two decades, accurate prediction of clinical events remains elusive. Atherosclerotic cardiovascular disease is the most common cause of death worldwide, and elucidating the mechanisms underlying the propagation and rupture of atherosclerotic plaques remains a key public health goal.