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  • Review Article
  • Published:

PET imaging of inflammation in atherosclerosis

Key Points

  • 18F-fluorodeoxyglucose (FDG) PET imaging of atherosclerosis is a reliable and reproducible measure of vascular inflammation, which can be used as a surrogate end point in clinical drug trials

  • The 18F-FDG PET signal indicates increased metabolic activity of macrophages, and probably also reflects contributions from local hypoxia and efficiency of tracer delivery by the microcirculation

  • Initial data suggest that 18F-FDG PET provides prognostic information above clinical and anatomical assessment alone; however, the outcome of large, prospective studies is awaited

  • Several tracers with established roles in cancer imaging (68Ga-DOTATATE, 11C-PK11195, and 18F-fluoromethylcholine) might be more-specific for vascular inflammation and better-suited to coronary artery imaging than 18F-FDG

Abstract

PET imaging of atherosclerosis can quantify several in vivo pathological processes occurring within the arterial system. 18F-fluorodeoxyglucose (FDG) is the most-commonly used PET tracer, with well-established roles in atherosclerosis imaging. In this context, the 18F-FDG signal largely reflects tracer uptake by plaque macrophages and, therefore, inflammation with smaller contributions from other resident cell types. As a marker of plaque vulnerability, the 18F-FDG PET signal can be used to help to identify patients at the highest risk of clinical events. 18F-FDG PET has also been used successfully as a surrogate end point in clinical trials of antiatherosclerotic therapies. Nonetheless, imaging atherosclerosis with 18F-FDG has several limitations. Most importantly, coronary artery imaging is problematic because 18F-FDG accumulates in all cells that metabolize glucose, and background myocardial uptake is generally greater than any signal originating from a plaque. To help to overcome these limitations, several novel PET tracers, which might be more-specifically targeted than 18F-FDG, have been tested in atherosclerosis imaging. These tracers are designed to track inflammation, hypoxia, neoangiogenesis, or active calcification, which are all precursors to plaque rupture and its clinical sequelae.

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Figure 1: The potential of scope PET atherosclerosis imaging.
Figure 2: 18F-fluorodeoxyglucose (FDG) carotid artery imaging.
Figure 3: Ex vivo 18F-fluorodeoxyglucose (FDG) microPET carotid plaque imaging.
Figure 4: Aortic 18F-FDG PET as a prognostic marker for cardiovascular disease.
Figure 5: 18F-sodium fluoride (NaF) coronary artery imaging.

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Acknowledgements

The authors are supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, UK. F.R.J. is also supported by a British Heart Foundation Clinical Research Fellowship and a Raymond and Beverley Sackler PhD Studentship. J.H.F.R. is additionally supported by the British Heart Foundation, the Evelyn Trust, and the Higher Education Funding Council for England.

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J.M.T. and J.H.F.R. researched, wrote, reviewed, and edited the manuscript. F.R.J. contributed substantially to the discussion of the scientific content with J.M.T. and J.H.F.R., reviewed the manuscript, and provided PET images.

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Correspondence to James H. F. Rudd.

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Tarkin, J., Joshi, F. & Rudd, J. PET imaging of inflammation in atherosclerosis. Nat Rev Cardiol 11, 443–457 (2014). https://doi.org/10.1038/nrcardio.2014.80

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