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YIA4 The Novel Alpha-V Beta-3 Integrin Positron Emission Tomography Radiotracer 18F-Fluciclatide is a Marker of Aortic Atherosclerosis Activity
  1. William Jenkins,
  2. Anna Vickers,
  3. Alison Fletcher,
  4. Anoushka Neale,
  5. Marc Dweck,
  6. Christophe Lucatelli,
  7. David Newby
  1. University of Edinburgh

Abstract

Introduction Intra-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.

Methods Forty-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.

Results There 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]).

Conclusion The 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.

  • Positron Emission Tomography
  • αvβ3 Integrin
  • Atherosclerosis

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