ObjectiveMaladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI.Methods18F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR.Results18F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p<0.001). There was no 18F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBRmean 0.71±0.06 vs 0.70±0.03, p=0.83). 18F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p<0.001) and subendocardial infarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=−0.20, p=0.38), 18F-fluciclatide uptake was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery.Conclusion18F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery.Trial registration numberNCT01813045; Post-results.

ObjectivesIntraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (αvβ3) integrin pathway. We investigated the applicability of the αvβ3-integrin receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide in assessing human aortic atherosclerosis.MethodsVascular 18F-fluciclatide binding was evaluated using ex vivo analysis of carotid endarterectomy samples with autoradiography and immunohistochemistry, and in vivo kinetic modelling following radiotracer administration. Forty-six subjects with a spectrum of atherosclerotic disease categorised as stable (n=27) or unstable (n=19; recent myocardial infarction) underwent PET and CT imaging of the thorax after administration of 229 (IQR 217–237) MBq 18F-fluciclatide. Thoracic aortic 18F-fluciclatide uptake was quantified on fused PET-CT images and corrected for blood-pool activity using the maximum tissue-to-background ratio (TBRmax). Aortic atherosclerotic burden was quantified by CT wall thickness, plaque volume and calcium scoring.Results18F-Fluciclatide uptake co-localised with regions of increased αvβ3 integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide vascular uptake was confirmed in vivo using kinetic modelling, and on static imaging correlated with measures of aortic atherosclerotic burden: wall thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and aortic CT calcium score (r=0.37, p=0.01). Patients with recent myocardial infarction had greater aortic 18F-fluciclatide uptake than those with stable disease (TBRmax 1.29 vs 1.21, p=0.02).ConclusionsIn vivo expression of αvβ3 integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of αvβ3 integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.

IntroductionIntra-plaque angiogenesis and inflammation are key promoters of plaque vulnerability. Angiogenic endothelial cells and macrophages express the integrin αvβ3. The novel RGD-based radiotracer 18F-Fluciclatide has high affinity for αvβ3 integrin and therefore may act as a surrogate marker of the unstable atherosclerotic plaque.MethodsForty-six subjects with a mixture of ischaemic heart disease and aortic stenosis, including 9 healthy subjects underwent CT-coronary angiography (CTCA) and combined PET/CT imaging of the thorax 40 min after the administration of 226 ± 13 mBq 18F-fluciclatide. Regions of interest were drawn around the thoracic aorta using serial axial slices on fused PET/CT images. 18F-Fluciclatide uptake in these regions was normalised for blood-pool activity in the superior vena cava using tissue to background ratio [TBR]. Reproducibility of this technique was assessed on 10 image-sets by two observers. Quantification and analysis of descending thoracic aortic atheroma on CTCA was performed using plaque analysis software.ResultsThere was a close correlation between 18F-fluciclatide uptake and the extent of atherosclerosis within the aorta on CTCA, as measured by wall thickness (r = 0.62 [0.31–0.81], p= <0.001] and total plaque burden (r = 0.60 [0.27–0.80], p = 0.001). Furthermore, aortic 18F-fluciclatide uptake (expressed as mean TBRmax) correlated with total aortic calcium score (AU) (r = 0.36 [0.05–0.60], p = 0.02) and was significantly greater in subjects with ischaemic heart disease (1.34 ± 0.03 vs 1.25 ± 0.03; p = 0.02) and hypercholesterolaemia (1.35 ± 0.03 vs 1.25 ± 0.03; p = 0.01).There were no significant age (r = 0.20(–0.12–0.47), p = 0.21) or sex related differences (1.34 ± 0.05 vs 1.29 ± 0.02, p = 0.24) and reproducibility analysis showed no fixed or proportional bias (0.07[–0.13–0.27]) with excellent intra-class correlation (0.98[0.92–1.0]).ConclusionThe quantification of αvβ3 integrin expression within the aorta using 18F-fluciclatide is a highly reproducible marker of atherosclerotic burden. This supports further work in establishing its role in the assessment of the unstable plaque.