Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

PET imaging of inflammation in atherosclerosis

Nature Reviews Cardiology volume 11, pages 443–457 (2014)Cite this article

Subjects

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

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.

References

  1. Nichols, M. et al. European Cardiovascular Disease Statistics 2012 Edition (European Heart Network and European Society of Cardiology, 2012).

    Google Scholar 

  2. Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2012).

    PubMed  Google Scholar 

  3. Go, A. S. et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129, e28–e292 (2014).

    PubMed  Google Scholar 

  4. Motoyama, S. et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J. Am. Coll. Cardiol. 54, 49–57 (2009).

    Article  PubMed  Google Scholar 

  5. Cai, J. et al. In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque. Circulation 112, 3437–3444 (2005).

    Article  PubMed  Google Scholar 

  6. Obaid, D. R. et al. Atherosclerotic plaque composition and classification identified by coronary computed tomography: assessment of computed tomography-generated plaque maps compared with virtual histology intravascular ultrasound and histology. Circ. Cardiovasc. Imaging 6, 655–664 (2013).

    Article  PubMed  Google Scholar 

  7. Osborn, E. A. & Jaffer, F. A. The advancing clinical impact of molecular imaging in CVD. JACC Cardiovasc. Imaging 6, 1327–1341 (2013).

    Article  PubMed  Google Scholar 

  8. Leuschner, F. & Nahrendorf, M. Molecular imaging of coronary atherosclerosis and myocardial infarction: considerations for the bench and perspectives for the clinic. Circ. Res. 108, 593–606 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vancraeynest, D., Pasquet, A., Roelants, V., Gerber, B. L. & Vanoverschelde, J. L. Imaging the vulnerable plaque. J. Am. Coll. Cardiol. 57, 1961–1979 (2011).

    Article  PubMed  Google Scholar 

  10. Quillard, T. & Libby, P. Molecular imaging of atherosclerosis for improving diagnostic and therapeutic development. Circ. Res. 111, 231–244 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wildgruber, M., Swirski, F. K. & Zernecke, A. Molecular imaging of inflammation in atherosclerosis. Theranostics 3, 865–884 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32, 2045–2051 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vita, J. A. Endothelial function. Circulation 124, e906–e912 (2011).

    Article  PubMed  Google Scholar 

  14. De Caterina, R. et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J. Clin. Invest. 96, 60–68 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Topper, J. N., Cai, J., Falb, D. & Gimbrone, M. A. Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc. Natl Acad. Sci. USA 93, 10417–10422 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Boring, L., Gosling, J., Cleary, M. & Charo, I. F. Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394, 894–897 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Falk, E. Pathogenesis of atherosclerosis. J. Am. Coll. Cardiol. 47, C7–C12 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Dutta, P. et al. Myocardial infarction accelerates atherosclerosis. Nature 487, 325–329 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Clinton, S. K. et al. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am. J. Pathol. 140, 301–316 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ross, R. & Glomset, J. A. Atherosclerosis and the arterial smooth muscle cell: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science 180, 1332–1339 (1973).

    Article  CAS  PubMed  Google Scholar 

  21. Stary, H. C. Composition and classification of human atherosclerotic lesions. Virchows Arch. A Pathol. Anat. Histopathol. 421, 277–290 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Libby, P. & Clinton, S. K. Cytokines as mediators of vascular pathology. Nouv. Rev. Fr. Hematol. 34 (Suppl.), S47–S53 (1992).

    PubMed  Google Scholar 

  23. Wexler, L. et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation 94, 1175–1192 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Fox, K. et al. Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur. Heart J. 27, 1341–1381 (2006).

    Article  PubMed  Google Scholar 

  25. Falk, E., Shah, P. K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Kaski, J. C., Chester, M. R., Chen, L. & Katritsis, D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology. Circulation 92, 2058–2065 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Libby, P. Molecular bases of the acute coronary syndromes. Circulation 91, 2844–2850 (1995).

    Article  CAS  PubMed  Google Scholar 

  28. Kolodgie, F. D. et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr. Opin. Cardiol. 16, 285–292 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Galis, Z. S., Sukhova, G. K., Lark, M. W. & Libby, P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin. Invest. 94, 2493–2503 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Barger, A. C., Beeuwkes, R. 3rd, Lainey, L. L. & Silverman, K. J. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N. Engl. J. Med. 310, 175–177 (1984).

    Article  CAS  PubMed  Google Scholar 

  31. Björnheden, T., Levin, M., Evaldsson, M. & Wiklund, O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler. Thromb. Vasc. Biol. 19, 870–876 (1999).

    Article  PubMed  Google Scholar 

  32. Virmani, R. et al. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler. Thromb. Vasc. Biol. 25, 2054–2061 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Hackett, D. D., Davies, G. G. & Maseri, A. A. Pre-existing coronary stenoses in patients with first myocardial infarction are not necessarily severe. Eur. Heart J. 9, 1317–1323 (1988).

    Article  CAS  PubMed  Google Scholar 

  34. Ambrose, J. A. et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J. Am. Coll. Cardiol. 12, 56–62 (1988).

    Article  CAS  PubMed  Google Scholar 

  35. Little, W. C. et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 78, 1157–1166 (1988).

    Article  CAS  PubMed  Google Scholar 

  36. Davies, M. J. & Thomas, A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N. Engl. J. Med. 310, 1137–1140 (1984).

    Article  CAS  PubMed  Google Scholar 

  37. Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Virmani, R., Burke, A. P., Farb, A. & Kolodgie, F. D. Pathology of the vulnerable plaque. J. Am. Coll. Cardiol. 47, C13–C18 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Narula, J. et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J. Am. Coll. Cardiol. 61, 1041–1051 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Stone, G. W. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Calvert, P. A. et al. Association between IVUS findings and adverse outcomes in patients with coronary artery disease: the VIVA (VH-IVUS in Vulnerable Atherosclerosis) Study. JACC Cardiovasc. Imaging 4, 894–901 (2011).

    Article  PubMed  Google Scholar 

  42. Varnava, A. M., Mills, P. G. & Davies, M. J. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 105, 939–943 (2002).

    Article  PubMed  Google Scholar 

  43. Smits, P. C. et al. Coronary artery disease: arterial remodelling and clinical presentation. Heart 82, 461–464 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mintz, G. S. et al. Atherosclerosis in angiographically 'normal' coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J. Am. Coll. Cardiol. 25, 1479–1485 (1995).

    Article  CAS  PubMed  Google Scholar 

  45. Moreno, P. R. et al. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 90, 775–778 (1994).

    Article  CAS  PubMed  Google Scholar 

  46. Woollard, K. J. & Geissmann, F. Monocytes in atherosclerosis: subsets and functions. Nat. Rev. Cardiol. 7, 77–86 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Calder, P. C., Dimitriadis, G. & Newsholme, P. Glucose metabolism in lymphoid and inflammatory cells and tissues. Curr. Opin. Clin. Nutr. Metab. Care 10, 531–540 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Martinez, F. O., Sica, A., Mantovani, A. & Locati, M. Macrophage activation and polarization. Front. Biosci. 13, 453–461 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Mantovani, A., Garlanda, C. & Locati, M. Macrophage diversity and polarization in atherosclerosis: a question of balance. Arterioscler. Thromb. Vasc. Biol. 29, 1419–1423 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Finn, A. V. et al. Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J. Am. Coll. Cardiol. 59, 166–177 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Ghattas, A., Griffiths, H. R., Devitt, A., Lip, G. Y. & Shantsila, E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J. Am. Coll. Cardiol. 62, 1541–1551 (2013).

    Article  CAS  PubMed  Google Scholar 

  52. Gupta, S. et al. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J. Clin. Invest. 99, 2752–2761 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pinderski, L. J. et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ. Res. 90, 1064–1071 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Butcher, M. J. & Galkina, E. V. Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets in the healthy and atherosclerosis-prone aorta. Front. Physiol. 3, 44 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pello, O. M., Silvestre, C., De Pizzol, M. & Andrés, V. A glimpse on the phenomenon of macrophage polarization during atherosclerosis. Immunobiology 216, 1172–1176 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Wilcox, J. N., Smith, K. M., Schwartz, S. M. & Gordon, D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc. Natl Acad. Sci. USA 86, 2839–2843 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mach, F., Schönbeck, U., Bonnefoy, J. Y., Pober, J. S. & Libby, P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation 96, 396–399 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Izquierdo-Garcia, D. et al. Comparison of methods for magnetic resonance-guided [18-F]fluorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods. Stroke 40, 86–93 (2009).

    Article  PubMed  Google Scholar 

  60. Burg, S. et al. Partial volume effect estimation and correction in the aortic vascular wall in PET imaging. Phys. Med. Biol. 58, 7527–7542 (2013).

    Article  CAS  PubMed  Google Scholar 

  61. Büther, F. et al. List mode-driven cardiac and respiratory gating in PET. J. Nucl. Med. 50, 674–681 (2009).

    Article  PubMed  Google Scholar 

  62. Fayad, H. J., Lamare, F., Le Rest, C. C., Bettinardi, V. & Visvikis, D. Generation of 4-dimensional CT images based on 4-dimensional PET-derived motion fields. J. Nucl. Med. 54, 631–638 (2013).

    Article  PubMed  Google Scholar 

  63. Mochizuki, T. et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J. Nucl. Med. 42, 1551–1555 (2001).

    CAS  PubMed  Google Scholar 

  64. Alavi, A. & Reivich, M. Guest editorial: the conception of FDG-PET imaging. Semin. Nucl. Med. 32, 2–5 (2002).

    Article  PubMed  Google Scholar 

  65. Rudd, J. H. et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 105, 2708–2711 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Bucerius, J. et al. Optimizing 18F-FDG PET/CT imaging of vessel wall inflammation: the impact of 18F-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels. Eur. J. Nucl. Med. Mol. Imaging 41, 369–383 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tawakol, A. et al. In vivo18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J. Am. Coll. Cardiol. 48, 1818–1824 (2006).

    Article  PubMed  Google Scholar 

  68. Pedersen, S. F. et al. Gene expression and 18FDG uptake in atherosclerotic carotid plaques. Nucl. Med. Commun. 31, 423–429 (2010).

    CAS  PubMed  Google Scholar 

  69. Græbe, M. et al. Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). Eur. J. Vasc. Endovasc. Surg. 37, 714–721 (2009).

    Article  PubMed  Google Scholar 

  70. Rosenbaum, D., Millon, A. & Fayad, Z. A. Molecular imaging in atherosclerosis: FDG PET. Curr. Atheroscler. Rep. 14, 429–437 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Folco, E. J. et al. Hypoxia but not inflammation augments glucose uptake in human macrophages: implications for imaging atherosclerosis with18Fluorine-labeled 2-deoxy-D-glucose positron emission tomography. J. Am. Coll. Cardiol. 58, 603–614 (2011).

    Article  CAS  PubMed  Google Scholar 

  72. Camici, P. G., Rimoldi, O. E., Gaemperli, O. & Libby, P. Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque. Eur. Heart J. 33, 1309–1317 (2012).

    Article  PubMed  Google Scholar 

  73. Pedersen, S. F. et al. Microvessel density but not neoangiogenesis is associated with 18F-FDG uptake in human atherosclerotic carotid plaques. Mol. Imaging Biol. 14, 384–392 (2011).

    Article  Google Scholar 

  74. Sluimer, J. C. et al. Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. J. Am. Coll. Cardiol. 51, 1258–1265 (2008).

    Article  CAS  PubMed  Google Scholar 

  75. Eltzschig, H. K. & Carmeliet, P. Hypoxia and inflammation. N. Engl. J. Med. 364, 656–665 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Boström, P. et al. Hypoxia converts human macrophages into triglyceride-loaded foam cells. Arterioscler. Thromb. Vasc. Biol. 26, 1871–1876 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Pedersen, S. F. et al. 18F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α. Am. J. Nucl. Med. Mol. Imaging 3, 384–392 (2013).

    PubMed  PubMed Central  Google Scholar 

  78. Ogawa, M., Nakamura, S., Saito, Y., Kosugi, M. & Magata, Y. What can be seen by 18F-FDG PET in atherosclerosis imaging? the effect of foam cell formation on 18F-FDG uptake to macrophages in vitro. J. Nucl. Med. 53, 55–58 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. Satomi, T. et al. Comparison of contrast agents for atherosclerosis imaging using cultured macrophages: FDG versus ultrasmall superparamagnetic iron oxide. J. Nucl. Med. 54, 999–1004 (2013).

    Article  CAS  PubMed  Google Scholar 

  80. Mahabadi, A. A. et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur. Heart J. 30, 850–856 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Hoeksema, M. A., Stöger, J. L. & de Winther, M. P. Molecular pathways regulating macrophage polarization: implications for atherosclerosis. Curr. Atheroscler. Rep. 14, 254–263 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Stöger, J. L., Goossens, P. & de Winther, M. P. J. Macrophage heterogeneity: relevance and functional implications in atherosclerosis. Curr. Vasc. Pharmacol. 8, 233–248 (2010).

    Article  PubMed  Google Scholar 

  83. Tavakoli, S., Zamora, D., Ullevig, S. & Asmis, R. Bioenergetic profiles diverge during macrophage polarization: implications for the interpretation of 18F-FDG PET imaging of atherosclerosis. J. Nucl. Med. 54, 1661–1667 (2013).

    Article  CAS  PubMed  Google Scholar 

  84. Vallabhajosula, S. et al. Imaging atherosclerotic macrophage density by positron emission tomography using F-18-fluorodeoxyglucose (FDG) [abstract 38P]. In Proceedings of the 43rd annual meeting of the Society of Nuclear Medicine. Denver, Colorado, June 3–5, 1996. J. Nucl. Med. 37 (5 Suppl.), 1P–346P (1996).

    Google Scholar 

  85. Helft, G. et al. Non-invasive in vivo imaging of atherosclerotic lesions using fluorine-18 deoxyglucose (18-FDG) pet correlates with macrophage content in a rabbit model. In 72nd Scientific Sessions of the American Heart Association. Atlanta, Georgia, USA. November 7–10, 1999. Circulation 100 (18 Suppl.), I1–I928 (1999).

    Google Scholar 

  86. Lederman, R. J. et al. Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl. Med. Commun. 22, 747–753 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Yun, M. et al. F-18 FDG uptake in the large arteries: a new observation. Clin. Nucl. Med. 26, 314–319 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Masteling, M. G. et al. High-resolution imaging of human atherosclerotic carotid plaques with micro18F-FDG PET scanning exploring plaque vulnerability. J. Nucl. Cardiol. 18, 1066–1075 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Rudd, J. H. et al. (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J. Am. Coll. Cardiol. 50, 892–896 (2007).

    Article  PubMed  Google Scholar 

  90. Rudd, J. H. et al. Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J. Nucl. Med. 49, 871–878 (2008).

    Article  PubMed  Google Scholar 

  91. Dunphy, M. P., Freiman, A., Larson, S. M. & Strauss, H. W. Association of vascular 18F-FDG uptake with vascular calcification. J. Nucl. Med. 46, 1278–1284 (2005).

    PubMed  Google Scholar 

  92. Wykrzykowska, J. et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J. Nucl. Med. 50, 563–568 (2009).

    Article  PubMed  Google Scholar 

  93. Nawaz, A. et al. Relation between popliteal-tibial artery atherosclerosis and global glycolytic metabolism in the affected diabetic foot: a pilot study using quantitative FDG-PET. J. Am. Podiatr. Med. Assoc. 102, 240–246 (2012).

    Article  PubMed  Google Scholar 

  94. Rudd, J. H. et al. Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study. Circ. Cardiovasc. Imaging 2, 107–115 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Tahara, N. et al. Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J. Am. Coll. Cardiol. 49, 1533–1539 (2007).

    Article  CAS  PubMed  Google Scholar 

  96. Wassélius, J. A., Larsson, S. A. & Jacobsson, H. FDG-accumulating atherosclerotic plaques identified with 18F-FDG-PET/CT in 141 patients. Mol. Imaging Biol. 11, 455–459 (2009).

    Article  PubMed  Google Scholar 

  97. Kim, T. N. et al. Vascular inflammation in patients with impaired glucose tolerance and type 2 diabetes: analysis with 18F-fluorodeoxyglucose positron emission tomography. Circ. Cardiovasc. Imaging 3, 142–148 (2010).

    Article  PubMed  Google Scholar 

  98. Noh, T. S. et al. Relation of carotid artery 18F-FDG uptake to C-reactive protein and Framingham risk score in a large cohort of asymptomatic adults. J. Nucl. Med. 54, 2070–2076 (2013).

    Article  CAS  PubMed  Google Scholar 

  99. Bural, G. G. et al. FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries. Eur. J. Nucl. Med. Mol. Imaging 35, 562–569 (2008).

    Article  PubMed  Google Scholar 

  100. Yoo, H. J. et al. Vascular inflammation stratified by C-reactive protein and low-density lipoprotein cholesterol levels: analysis with 18F-FDG PET. J. Nucl. Med. 52, 10–17 (2011).

    Article  CAS  PubMed  Google Scholar 

  101. Wu, Y.-W. et al. Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1. J. Nucl. Med. 48, 227–233 (2007).

    CAS  PubMed  Google Scholar 

  102. Choi, H. Y. et al. Association of adiponectin, resistin, and vascular inflammation: analysis with 18F-fluorodeoxyglucose positron emission tomography. Arterioscler. Thromb. Vasc. Biol. 31, 944–949 (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Græbe, M., Pedersen, S. F., Højgaard, L., Kjær, A. & Sillesen, H. 18FDG PET and ultrasound echolucency in carotid artery plaques. JACC Cardiovasc. Imaging 3, 289–295 (2010).

    Article  PubMed  Google Scholar 

  104. Silvera, S. S. et al. Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis 207, 139–143 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Figueroa, A. L. et al. Distribution of inflammation within carotid atherosclerotic plaques with high-risk morphological features: a comparison between positron emission tomography activity, plaque morphology, and histopathology. Circ. Cardiovasc. Imaging 5, 69–77 (2012).

    Article  PubMed  Google Scholar 

  106. Joly, L. et al. Aortic inflammation, as assessed by hybrid FDG-PET/CT imaging, is associated with enhanced aortic stiffness in addition to concurrent calcification. Eur. J. Nucl. Med. Mol. Imaging 36, 979–985 (2009).

    Article  PubMed  Google Scholar 

  107. Rudd, J. H. et al. Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study. Circ. Cardiovasc. Imaging 2, 107–115 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Menezes, L. J. et al. Investigating vulnerable atheroma using combined 18F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation. J. Nucl. Med. 52, 1698–1703 (2011).

    Article  PubMed  Google Scholar 

  109. Ben-Haim, S., Kupzov, E., Tamir, A. & Israel, O. Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. J. Nucl. Med. 45, 1816–1821 (2004).

    PubMed  Google Scholar 

  110. Cocker, M. S. et al. Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see. J. Nucl. Cardiol. 19, 1211–1225 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Bucerius, J. et al. Arterial and fat tissue inflammation are highly correlated: a prospective (18)F-FDG PET/CT study. Eur. J. Nucl. Med. Mol. Imaging 41, 934–945 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Grundy, S. M. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation 105, 2696–2698 (2002).

    Article  PubMed  Google Scholar 

  113. Apovian, C. M. et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler. Thromb. Vasc. Biol. 28, 1654–1659 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rosito, G. A. et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 117, 605–613 (2008).

    Article  PubMed  Google Scholar 

  115. Gorter, P. M. et al. Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography. Am. J. Cardiol. 102, 380–385 (2008).

    Article  CAS  PubMed  Google Scholar 

  116. Kim, E. J., Kim, S., Seo, H. S. & Kang, D. O. The metabolic activity of the spleen and bone marrow in patients with acute myocardial infarction evaluated by 18F-FDG PET imaging. Circ. Cardiovasc. Imaging http://dx.doi.org/10.1161/CIRCIMAGING.113.001093.

  117. Arauz, A., Hoyos, L., Zenteno, M., Mendoza, R. & Alexanderson, E. Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography. Pilot study. Clin. Neurol. Neurosurg. 109, 409–412 (2007).

    Article  PubMed  Google Scholar 

  118. Davies, J. R. et al. Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke 36, 2642–2647 (2005).

    Article  PubMed  Google Scholar 

  119. Moustafa, R. R. et al. Carotid plaque inflammation is associated with cerebral microembolism in patients with recent transient ischemic attack or stroke: a pilot study. Circ. Cardiovasc. Imaging 3, 536–541 (2010).

    Article  PubMed  Google Scholar 

  120. Marnane, M. et al. Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence. Ann. Neurol. 71, 709–718 (2012).

    Article  PubMed  Google Scholar 

  121. Paulmier, B. et al. Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J. Nucl. Cardiol. 15, 209–217 (2008).

    Article  PubMed  Google Scholar 

  122. Rominger, A. et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J. Nucl. Med. 50, 1611–1620 (2009).

    Article  PubMed  Google Scholar 

  123. Grandpierre, S. et al. Arterial foci of F-18 fluorodeoxyglucose are associated with an enhanced risk of subsequent ischemic stroke in cancer patients: a case–control pilot study. Clin. Nucl. Med. 36, 85–90 (2011).

    Article  PubMed  Google Scholar 

  124. Figueroa, A. L. et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. JACC Cardiovasc. Imaging 6, 1250–1259 (2013).

    Article  PubMed  Google Scholar 

  125. Ryu, Y. et al. Long-term changes of aortic 18F-FDG uptake and calcification in health-screening subjects. Ann. Nucl. Med. 27, 239–246 (2012).

    Article  CAS  PubMed  Google Scholar 

  126. Muntendam, P., McCall, C., Sanz, J., Falk, E. & Fuster, V. The BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease—study design and objectives. Am. Heart J. 160, 49–57. e1 (2010).

    Article  PubMed  Google Scholar 

  127. Fernández-Ortiz, A. et al. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study: rationale and design. Am. Heart J. 166, 990–998 (2013).

    Article  PubMed  Google Scholar 

  128. Lee, S. J. et al. Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction. J. Nucl. Med. 49, 1277–1282 (2008).

    Article  CAS  PubMed  Google Scholar 

  129. Tahara, N. et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J. Am. Coll. Cardiol. 48, 1825–1831 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. Rudd, J. H., Machac, J. & Fayad, Z. A. Simvastatin and plaque inflammation. J. Am. Coll. Cardiol. 49, 1991 (2007).

    Article  PubMed  Google Scholar 

  131. Ishii, H. et al. Comparison of atorvastatin 5 and 20 mg/d for reducing F-18 fluorodeoxyglucose uptake in atherosclerotic plaques on positron emission tomography/computed tomography: a randomized, investigator-blinded, open-label, 6-month study in Japanese adults scheduled for percutaneous coronary intervention. Clin. Ther. 32, 2337–2347 (2010).

    Article  CAS  PubMed  Google Scholar 

  132. Wu, Y.-W. et al. The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur. J. Nucl. Med. Mol. Imaging 39, 399–407 (2011).

    Article  CAS  PubMed  Google Scholar 

  133. Tawakol, A. et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J. Am. Coll. Cardiol. 62, 909–917 (2013).

    Article  CAS  PubMed  Google Scholar 

  134. Subramanian, S. et al. High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins. J. Am. Coll. Cardiol. 62, 2382–2391 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Potter, K. et al. Effect of long-term homocysteine reduction with B vitamins on arterial wall inflammation assessed by fluorodeoxyglucose positron emission tomography: a randomised double-blind, placebo-controlled trial. Cerebrovasc. Dis. 27, 259–265 (2009).

    Article  CAS  PubMed  Google Scholar 

  136. Elkhawad, M. et al. Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis. JACC Cardiovasc. Imaging 5, 911–922 (2012).

    Article  PubMed  Google Scholar 

  137. Tawakol, A. et al. Effect of treatment for 12 weeks with rilapladib, a lipoprotein-associated phospholipase A2 inhibitor, on arterial inflammation as assessed with (18)f-fluorodeoxyglucose-positron emission tomography imaging. J. Am. Coll. Cardiol. 63, 86–88 (2014).

    Article  CAS  PubMed  Google Scholar 

  138. Shaddinger, B. C. et al. Platelet aggregation unchanged by lipoprotein-associated phospholipase A2 inhibition: results from an in vitro study and two randomized phase I trials. PLoS ONE 27, e83094 (2014).

    Article  CAS  Google Scholar 

  139. Mäki-Petäjä, K. M. et al. Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation 126, 2473–2480 (2012).

    Article  CAS  PubMed  Google Scholar 

  140. Ridker, P. M., Thuren, T., Zalewski, A. & Libby, P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Am. Heart J. 162, 597–605 (2011).

    Article  CAS  PubMed  Google Scholar 

  141. Everett, B. M. et al. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am. Heart J. 166, 199–207. e15 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Fayad, Z. A. et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet 378, 1547–1559 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Schwartz, G. G. et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 367, 2089–2099 (2012).

    Article  CAS  PubMed  Google Scholar 

  144. Font, M. A. et al. Imaging of early inflammation in low-to-moderate carotid stenosis by 18-FDG-PET. Front. Biosci. (Landmark Ed.) 14, 3352–3360 (2009).

    Article  CAS  Google Scholar 

  145. Wassélius, J., Larsson, S. & Jacobsson, H. Time-to-time correlation of high-risk atherosclerotic lesions identified with [(18)F]-FDG-PET/CT. Ann. Nucl. Med. 23, 59–64 (2009).

    Article  CAS  PubMed  Google Scholar 

  146. Ben-Haim, S., Kupzov, E., Tamir, A., Frenkel, A. & Israel, O. Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies. J. Nucl. Cardiol. 13, 791–800 (2006).

    Article  PubMed  Google Scholar 

  147. Saam, T. et al. Association of inflammation of the left anterior descending coronary artery with cardiovascular risk factors, plaque burden and pericardial fat volume: a PET/CT study. Eur. J. Nucl. Med. Mol. Imaging 37, 1203–1212 (2010).

    Article  PubMed  Google Scholar 

  148. Williams, G. & Kolodny, G. M. Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: a preliminary study. Nucl. Med. Commun. 30, 287–291 (2009).

    Article  CAS  PubMed  Google Scholar 

  149. Rogers, I. S. et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc. Imaging 3, 388–397 (2010).

    Article  PubMed  Google Scholar 

  150. Cheng, V. Y. et al. Coronary arterial 18F-FDG uptake by fusion of PET and coronary CT angiography at sites of percutaneous stenting for acute myocardial infarction and stable coronary artery disease. J. Nucl. Med. 53, 575–583 (2012).

    Article  CAS  PubMed  Google Scholar 

  151. Joshi, N. V. et al. (18)F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 383, 705–713 (2014).

    Article  PubMed  Google Scholar 

  152. Morooka, M. et al. Long fasting is effective in inhibiting physiological myocardial 18F-FDG uptake and for evaluating active lesions of cardiac sarcoidosis. EJNMMI Res. 4, 1 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Rogers, I. S. & Tawakol, A. Imaging of coronary inflammation with FDG-PET: feasibility and clinical hurdles. Curr. Cardiol. Rep. 13, 138–144 (2011).

    Article  PubMed  Google Scholar 

  154. Rudd, J. H. et al. Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? J. Am. Coll. Cardiol. 55, 2527–2535 (2010).

    Article  PubMed  Google Scholar 

  155. Patel, Y. C. Somatostatin and its receptor family. Front. Neuroendocrinol. 20, 157–198 (1999).

    Article  CAS  PubMed  Google Scholar 

  156. Boy, C. et al. 68Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax. Eur. J. Nucl. Med. Mol. Imaging 38, 1224–1236 (2011).

    Article  CAS  PubMed  Google Scholar 

  157. Armani, C., Catalani, E., Balbarini, A., Bagnoli, P. & Cervia, D. Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages. J. Leukoc. Biol. 81, 845–855 (2006).

    Article  CAS  PubMed  Google Scholar 

  158. Adams, R. L., Adams, I. P., Lindow, S. W., Zhong, W. & Atkin, S. L. Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium. Br. J. Cancer 92, 1493–1498 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Dalm, V. A. et al. Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. Am. J. Physiol. Endocrinol. Metab. 285, E344–E353 (2003).

    Article  CAS  PubMed  Google Scholar 

  160. Rominger, A. et al. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J. Nucl. Med. 51, 193–197 (2010).

    Article  PubMed  Google Scholar 

  161. Li, X. et al. 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with 18F-FDG, calcium burden and risk factors. EJNMMI Res. 2, 52 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Li, X. et al. Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice. Atherosclerosis 230, 33–39 (2013).

    Article  CAS  PubMed  Google Scholar 

  163. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  164. Laitinen, I. et al. Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques. Eur. J. Nucl. Med. Mol. Imaging 36, 73–80 (2009).

    Article  CAS  PubMed  Google Scholar 

  165. Fujimura, Y. et al. Increased peripheral benzodiazepine receptors in arterial plaque of patients with atherosclerosis: an autoradiographic study with [(3)H]PK 11195. Atherosclerosis 201, 108–111 (2008).

    Article  CAS  PubMed  Google Scholar 

  166. Bird, J. L. et al. Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis. Atherosclerosis 210, 388–391 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Pugliese, F. et al. Imaging of vascular inflammation with [11C]-PK11195 and positron emission tomography/computed tomography angiography. J. Am. Coll. Cardiol. 56, 653–661 (2010).

    Article  PubMed  Google Scholar 

  168. Gaemperli, O. et al. Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography. Eur. Heart J. 33, 1902–1910 (2012).

    Article  CAS  PubMed  Google Scholar 

  169. Shalhoub, J., Oskrochi, Y., Davies, A. H. & Owen, D. R. Clinical assessment of carotid atherosclerosis inflammation by positron emission tomography. Curr. Mol. Med. 13, 1646–1652 (2013).

    Article  CAS  PubMed  Google Scholar 

  170. Owen, D. R., Lindsay, A. C., Choudhury, R. P. & Fayad, Z. A. Imaging of atherosclerosis. Annu. Rev. Med. 62, 25–40 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Laitinen, I. E. et al. Uptake of 11C-choline in mouse atherosclerotic plaques. J. Nucl. Med. 51, 798–802 (2010).

    Article  PubMed  Google Scholar 

  172. Matter, C. M. 18F-choline images murine atherosclerotic plaques ex vivo. Arterioscler. Thromb. Vasc. Biol. 26, 584–589 (2005).

    Article  CAS  PubMed  Google Scholar 

  173. Bucerius, J. et al. Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans—first results. Eur. J. Nucl. Med. Mol. Imaging 35, 815–820 (2008).

    Article  PubMed  Google Scholar 

  174. Kato, K. et al. Evaluation and comparison of 11C-choline uptake and calcification in aortic and common carotid arterial walls with combined PET/CT. Eur. J. Nucl. Med. Mol. Imaging 36, 1622–1628 (2009).

    Article  CAS  PubMed  Google Scholar 

  175. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  176. Marsch, E., Sluimer, J. C. & Daemen, M. J. Hypoxia in atherosclerosis and inflammation. Curr. Opin. Lipidol. 24, 393–400 (2013).

    Article  CAS  PubMed  Google Scholar 

  177. Mateo, J., Izquierdo-Garcia, D., Badimon, J. J., Fayad, Z. A. & Fuster, V. Noninvasive assessment of hypoxia in rabbit advanced atherosclerosis using 18F-fluoromisonidazole PET imaging. Circ. Cardiovasc. Imaging 7, 312–320 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Joshi, F. R. et al. Imaging of hypoxia and inflammation in carotid atherosclerosis with 18F-fluoromisonidazole and 18F-fluorodeoxyglucose positron emission tomography (abstract 14673). Circulation 128 (22 Suppl.) A14673 (2013).

    Google Scholar 

  179. Paeng, J. C. et al. Feasibility and kinetic characteristics of (68)Ga-NOTA-RGD PET for in vivo atherosclerosis imaging. Ann. Nucl. Med. 27, 847–854 (2013).

    Article  CAS  PubMed  Google Scholar 

  180. Beer, A. J. et al. PET/CT imaging of integrin αvβ3 expression in human carotid atherosclerosis. JACC Cardiovasc. Imaging 7, 178–187 (2014).

    Article  PubMed  Google Scholar 

  181. Kataoka, Y. et al. Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: insights from serial intravascular ultrasound. J. Am. Coll. Cardiol. 59, 1592–1597 (2012).

    Article  PubMed  Google Scholar 

  182. Vengrenyuk, Y. et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc. Natl Acad. Sci. USA 103, 14678–14683 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of Cambridge, Box 110, Addenbrooke's Centre for Cardiovascular Investigation, Hills Road, Cambridge, CB2 2QQ, UK

    Jason M. Tarkin, Francis R. Joshi & James H. F. Rudd

Authors
  1. Jason M. Tarkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francis R. Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James H. F. Rudd
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to James H. F. Rudd.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2014.80

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing