Display options
Share it on

Front Physiol. 2020 Oct 22;11:511391. doi: 10.3389/fphys.2020.511391. eCollection 2020.

Imaging Atherosclerosis by PET, With Emphasis on the Role of FDG and NaF as Potential Biomarkers for This Disorder.

Frontiers in physiology

Michael Mayer, Austin J Borja, Emily C Hancin, Thomas Auslander, Mona-Elisabeth Revheim, Mateen C Moghbel, Thomas J Werner, Abass Alavi, Chamith S Rajapakse

Affiliations

  1. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.
  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
  3. Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.
  4. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
  5. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  6. Department of Radiology, Massachusetts General Hospital, Boston, MA, United States.
  7. Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.

PMID: 33192540 PMCID: PMC7642524 DOI: 10.3389/fphys.2020.511391

Abstract

Molecular imaging has emerged in the past few decades as a novel means to investigate atherosclerosis. From a pathophysiological perspective, atherosclerosis is characterized by microscopic inflammation and microcalcification that precede the characteristic plaque buildup in arterial walls detected by traditional assessment methods, including anatomic imaging modalities. These processes of inflammation and microcalcification are, therefore, prime targets for molecular detection of atherosclerotic disease burden. Imaging with positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) can non-invasively assess arterial inflammation and microcalcification, respectively. FDG uptake reflects glucose metabolism, which is particularly increased in atherosclerotic plaques retaining macrophages and undergoing hypoxic stress. By contrast, NaF uptake reflects the exchange of hydroxyl groups of hydroxyapatite crystals for fluoride producing fluorapatite, a key biochemical step in calcification of atherosclerotic plaque. Here we review the existing literature on FDG and NaF imaging and their respective values in investigating the progression of atherosclerotic disease. Based on the large volume of data that have been introduced to the literature and discussed in this review, it is clear that PET imaging will have a major role to play in assessing atherosclerosis in the major and coronary arteries. However, it is difficult to draw definitive conclusions on the potential role of FDG in investigating atherosclerosis given the vast number of studies with different designs, image acquisition methods, analyses, and interpretations. Our experience in this domain of research has suggested that NaF may be the tool of choice over FDG in assessing atherosclerosis, especially in the setting of coronary artery disease (CAD). Specifically, global NaF assessment appears to be superior in detecting plaques in tissues with high background FDG activity, such as the coronary arteries.

Copyright © 2020 Mayer, Borja, Hancin, Auslander, Revheim, Moghbel, Werner, Alavi and Rajapakse.

Keywords: PET; atherosclerosis; fluorodeoxyglucose; molecular imaging; sodium fluoride

References

  1. Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2228-2235 - PubMed
  2. Circulation. 1992 Dec;86(6 Suppl):III30-42 - PubMed
  3. Cardiovasc Res. 1999 Feb;41(2):334-44 - PubMed
  4. J Nucl Med. 2015 Oct;56(10):1534-40 - PubMed
  5. Angiology. 2007 Oct-Nov;58(5):513-22 - PubMed
  6. Eur J Nucl Med Mol Imaging. 2008 Mar;35(3):562-9 - PubMed
  7. Cardiol J. 2018 Jul 16;: - PubMed
  8. J Am Coll Cardiol. 2019 May 21;73(19):2489-2491 - PubMed
  9. J Nucl Cardiol. 2014 Apr;21(2):293-304 - PubMed
  10. Semin Nucl Med. 2002 Jan;32(1):70-6 - PubMed
  11. Clin Nucl Med. 2001 Apr;26(4):314-9 - PubMed
  12. Nat Med. 2011 Nov 07;17(11):1410-22 - PubMed
  13. JACC Cardiovasc Imaging. 2019 Feb;12(2):370-372 - PubMed
  14. Ann Neurol. 2012 May;71(5):709-18 - PubMed
  15. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018 Mar;162(1):10-17 - PubMed
  16. J Nucl Cardiol. 2019 Feb 27;: - PubMed
  17. Nat Commun. 2015 Jul 07;6:7495 - PubMed
  18. Hell J Nucl Med. 2011 May-Aug;14(2):114-20 - PubMed
  19. Mol Imaging Biol. 2014 Jun;16(3):330-9 - PubMed
  20. Eur J Nucl Med Mol Imaging. 2020 Jul;47(7):1678-1687 - PubMed
  21. Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1715-1723 - PubMed
  22. J Am Coll Cardiol. 2003 Feb 19;41(4 Suppl S):15S-22S - PubMed
  23. Lancet. 2012 Dec 15;380(9859):2095-128 - PubMed
  24. Hell J Nucl Med. 2019 Jan-Apr;22(1):14-19 - PubMed
  25. Nucl Med Commun. 2013 Sep;34(9):860-7 - PubMed
  26. J Thorac Imaging. 2011 Feb;26(1):54-62 - PubMed
  27. JACC Cardiovasc Imaging. 2018 Aug;11(8):1173-1186 - PubMed
  28. Can J Cardiol. 2017 Mar;33(3):303-312 - PubMed
  29. Semin Nucl Med. 2018 Nov;48(6):488-497 - PubMed
  30. J Nucl Med. 2005 Aug;46(8):1278-84 - PubMed
  31. Atherosclerosis. 2018 Jan;268:49-54 - PubMed
  32. J Nucl Cardiol. 2014 Jun;21(3):588-97 - PubMed
  33. PET Clin. 2019 Apr;14(2):197-209 - PubMed
  34. J Nucl Med. 2009 Apr;50(4):563-8 - PubMed
  35. JACC Cardiovasc Imaging. 2013 Dec;6(12):1250-9 - PubMed
  36. Circ Cardiovasc Imaging. 2017 Mar;10(3): - PubMed
  37. JACC Cardiovasc Imaging. 2012 Jan;5(1):38-45 - PubMed
  38. AJR Am J Roentgenol. 2008 Feb;190(2):W151-6 - PubMed
  39. Korean Circ J. 2018 Jul;48(7):591-601 - PubMed
  40. Circ Cardiovasc Imaging. 2013 Sep;6(5):747-54 - PubMed
  41. Nucl Med Biol. 2006 Nov;33(8):1037-43 - PubMed
  42. J Am Coll Cardiol. 2020 Jun 23;75(24):3061-3074 - PubMed
  43. Mol Imaging Biol. 2013 Jun;15(3):345-52 - PubMed
  44. J Nucl Med. 2010 Jun;51(6):862-5 - PubMed
  45. Eur J Nucl Med Mol Imaging. 2017 Feb;44(2):249-258 - PubMed
  46. Int J Cardiovasc Imaging. 2014 Feb;30(2):439-47 - PubMed
  47. Nat Rev Cardiol. 2019 Dec;16(12):727-744 - PubMed
  48. Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2493-2498 - PubMed
  49. Nucl Med Commun. 2016 Aug;37(8):833-6 - PubMed
  50. JACC Cardiovasc Imaging. 2020 Apr;13(4):1008-1017 - PubMed
  51. J Am Coll Cardiol. 2018 Jan 23;71(3):263-275 - PubMed
  52. J Nucl Med. 2009 Oct;50(10):1611-20 - PubMed
  53. EJNMMI Res. 2012 Jul 18;2(1):39 - PubMed
  54. Circulation. 2002 Jun 11;105(23):2708-11 - PubMed
  55. Eur J Nucl Med Mol Imaging. 2015 Aug;42(9):1414-22 - PubMed
  56. Circ Cardiovasc Imaging. 2012 Jan;5(1):69-77 - PubMed
  57. Lancet. 2014 Feb 22;383(9918):705-13 - PubMed
  58. J Am Coll Cardiol. 2006 Nov 7;48(9):1818-24 - PubMed
  59. JACC Cardiovasc Imaging. 2020 Jul;13(7):1549-1560 - PubMed
  60. J Nucl Med. 1993 Oct;34(10):1681-7 - PubMed
  61. N Engl J Med. 2005 Apr 21;352(16):1685-95 - PubMed
  62. J Nucl Cardiol. 2018 Oct;25(5):1742-1756 - PubMed
  63. Nucl Med Commun. 2017 Nov;38(11):1007-1014 - PubMed
  64. J Am Coll Cardiol. 2012 Apr 24;59(17):1549-50 - PubMed
  65. J Nucl Med. 2015 Apr;56(4):552-9 - PubMed
  66. Circ Res. 2014 Sep 12;115(7):662-7 - PubMed
  67. Radiology. 2003 Dec;229(3):831-7 - PubMed
  68. J Nucl Med. 2011 Mar;52(3):362-8 - PubMed
  69. J Nucl Cardiol. 2008 Mar-Apr;15(2):209-17 - PubMed
  70. Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):129-140 - PubMed
  71. J Nucl Med. 2004 Nov;45(11):1816-21 - PubMed
  72. Circ Res. 2016 Feb 19;118(4):620-36 - PubMed
  73. Int J Cardiovasc Imaging. 2013 Dec;29(8):1899-908 - PubMed
  74. Eur J Nucl Med Mol Imaging. 2018 Nov;45(12):2190-2200 - PubMed
  75. J Nucl Med. 2004 Jul;45(7):1245-50 - PubMed
  76. Hell J Nucl Med. 2015 Jan-Apr;18(1):5-10 - PubMed
  77. JACC Cardiovasc Imaging. 2016 Oct;9(10):1198-1207 - PubMed

Publication Types