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PET/CT Imaging of Inflammation and Calcification in CAVD: Clinical Studies

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Cardiovascular Imaging

Abstract

Molecular imaging using positron-emission tomography combined with computed tomography (PET/CT) to demonstrate aortic valve inflammation (18F-FDG) and calcification (18F-NaF) in CAVD holds major promise. Several studies have now shown that these PET radiotracers are able to reproducibly quantify these two important intra-valvular pathological processes. This development represents an exciting opportunity not only to explore CAVD pathology in vivo and predict disease progression but also to provide the means of gaining early signal of efficacy in phase II trials of novel drug interventions.

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References

  1. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro heart survey on valvular heart disease. Eur Heart J. 2003;24:1231–43.

    Article  PubMed  Google Scholar 

  2. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005–11. doi:10.1016/S0140-6736(06)69208-8.

    Article  PubMed  Google Scholar 

  3. Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352:2389–97. doi:10.1056/NEJMoa043876.

    Article  CAS  PubMed  Google Scholar 

  4. Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343–56. doi:10.1056/NEJMoa0804602.

    Article  PubMed  Google Scholar 

  5. Chan KL, Teo K, Dumesnil JG, et al. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. Circulation. 2010;121:306–14. doi:10.1161/CIRCULATIONAHA.109.900027.

    Article  CAS  PubMed  Google Scholar 

  6. Miller JD, Weiss RM, Heistad DD. Calcific aortic valve stenosis: methods, models, and mechanisms. Circ Res. 2011;108:1392–412. doi:10.1161/CIRCRESAHA.110.234138.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Dweck MR, Jones C, Joshi NV, et al. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012;125:76–86. doi:10.1161/CIRCULATIONAHA.111.051052.

    Article  CAS  PubMed  Google Scholar 

  8. New SEP, Aikawa E. Role of extracellular vesicles in de novo mineralization: an additional novel mechanism of cardiovascular calcification. Arterioscler Thromb Vasc Biol. 2013;33:1753–8. doi:10.1161/ATVBAHA.112.300128.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol. 2012;60:1854–63. doi:10.1016/j.jacc.2012.02.093.

    Article  PubMed  Google Scholar 

  10. New SEP, Aikawa E. Cardiovascular calcification. Circ J. 2011;75:1305–13. doi:10.1253/circj.CJ-11-0395.

    Article  CAS  PubMed  Google Scholar 

  11. Reivich M, Kuhl D, Wolf A, et al. Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurol Scand Suppl. 1977;64:190–1.

    CAS  PubMed  Google Scholar 

  12. Rudd JHF. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105:2708–11. doi:10.1161/01.CIR.0000020548.60110.76.

    Article  CAS  PubMed  Google Scholar 

  13. Fayad ZA, Mani V, Woodward M, et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378:1547–59. doi:10.1016/S0140-6736(11)61383-4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Tawakol A, Migrino RQ, Hoffmann U, et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol. 2005;12:294–301. doi:10.1016/j.nuclcard.2005.03.002.

    Article  PubMed  Google Scholar 

  15. Tawakol A, Migrino RQ, Bashian GG, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–24. doi:10.1016/j.jacc.2006.05.076.

    Article  PubMed  Google Scholar 

  16. Kaim AH, Weber B, Kurrer MO, et al. Autoradiographic quantification of 18F-FDG uptake in experimental soft-tissue abscesses in rats. Radiology. 2002;223:446–51. doi:10.1148/radiol.2232010914.

    Article  PubMed  Google Scholar 

  17. Babior BM. The respiratory burst of phagocytes. J Clin Invest. 1984;73:599–601. doi:10.1172/JCI111249.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Joshi F, Rosenbaum D, Bordes S, Rudd JHF. Vascular imaging with positron emission tomography. J Intern Med. 2011;270:99–109. doi:10.1111/j.1365-2796.2011.02392.x.

    Article  CAS  PubMed  Google Scholar 

  19. Folco EJ, Sheikine Y, Rocha VZ, et al. Hypoxia but not inflammation augments glucose uptake in human macrophages. J Am Coll Cardiol. 2011;58:603–14. doi:10.1016/j.jacc.2011.03.044.

    Article  CAS  PubMed  Google Scholar 

  20. Pedersen SF, Graebe M, Hag AMF, 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. 2013;3:384.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Tawakol A, Fayad ZA, Mogg R, 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. 2013;62:909–17. doi:10.1016/j.jacc.2013.04.066.

    Article  CAS  PubMed  Google Scholar 

  22. Marincheva-Savcheva G, Subramanian S, Qadir S, et al. Imaging of the aortic valve using fluorodeoxyglucose positron emission tomography increased valvular fluorodeoxyglucose uptake in aortic stenosis. J Am Coll Cardiol. 2011;57:2507–15. doi:10.1016/j.jacc.2010.12.046.

    Article  PubMed  Google Scholar 

  23. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827–32.

    Article  CAS  PubMed  Google Scholar 

  24. Aikawa E, Otto CM. Look more closely at the valve: imaging calcific aortic valve disease. Circulation. 2012;125:9–11. doi:10.1161/CIRCULATIONAHA.111.073452.

    Article  PubMed  Google Scholar 

  25. Dweck MR, Jenkins WSA, Vesey AT, et al. 18F-NaF uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014. doi:10.1161/CIRCIMAGING.113.001508.

    PubMed  Google Scholar 

  26. Joshi NV, Vesey AT, Williams MC, et al. (18)F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2013. doi:10.1016/S0140-6736(13)61754-7.

    PubMed  Google Scholar 

  27. Blau M, Ganatra R, Bender MA. 18F-fluoride for bone imaging. Semin Nucl Med. 1972;2:31–7.

    Article  CAS  PubMed  Google Scholar 

  28. Brenner W, Vernon C, Muzi M, et al. Comparison of different quantitative approaches to 18F-fluoride PET scans. J Nucl Med. 2004;45:1493–500.

    CAS  PubMed  Google Scholar 

  29. Cook GJ, Lodge MA, Blake GM, et al. Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women. J Bone Miner Res. 2000;15:763–9. doi:10.1359/jbmr.2000.15.4.763.

    Article  CAS  PubMed  Google Scholar 

  30. Cook GJR, Blake GM, Marsden PK, et al. Quantification of skeletal kinetic indices in Paget's disease using Dynamic 18F-fluoride positron emission tomography. J Bone Miner Res. 2002;17:854–9. doi:10.1359/jbmr.2002.17.5.854.

    Google Scholar 

  31. Even-Sapir E, Mishani E, Flusser G, Metser U. 18F-fluoride positron emission tomography and positron emission tomography/computed tomography. Semin Nucl Med. 2007;37:462–9. doi:10.1053/j.semnuclmed.2007.07.002.

    Article  PubMed  Google Scholar 

  32. Frost ML, Blake GM, Park-Holohan SJ, et al. Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism. J Nucl Med. 2008;49:700–7. doi:10.2967/jnumed.107.046987.

    Article  PubMed  Google Scholar 

  33. Frost ML, Cook GJR, Blake GM, et al. A prospective study of risedronate on regional bone metabolism and blood flow at the lumbar spine measured by 18F-fluoride positron emission tomography. J Bone Miner Res. 2003;18:2215–22. doi:10.1359/jbmr.2003.18.12.2215.

    Article  CAS  PubMed  Google Scholar 

  34. Frost ML, Cook GJR, Blake GM, et al. The relationship between regional bone turnover measured using 18F-fluoride positron emission tomography and changes in BMD is equivalent to that seen for biochemical markers of bone turnover. J Clin Densitom. 2007;10:46–54. doi:10.1016/j.jocd.2006.10.006.

    Article  PubMed  Google Scholar 

  35. Frost ML, Fogelman I, Blake GM, et al. Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis. J Bone Miner Res. 2004;19:1797–804. doi:10.1359/JBMR.040818.

    Article  CAS  PubMed  Google Scholar 

  36. Hawkins RA, Choi Y, Huang SC, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992;33:633–42.

    CAS  PubMed  Google Scholar 

  37. Installe J, Nzeusseu A, Bol A, et al. F-18-fluoride PET for monitoring therapeutic response in Paget's disease of bone. J Nucl Med. 2005;46:1650–8.

    CAS  PubMed  Google Scholar 

  38. Messa C, Goodman WG, Hoh CK, et al. Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry. J Clin Endocrinol Metab. 1993;77:949–55. doi:10.1210/jcem.77.4.8408470.

    CAS  PubMed  Google Scholar 

  39. Piert M, Zittel TT, Becker GA, et al. Assessment of porcine bone metabolism by dynamic [F-18]fluoride ion PET: Correlation with bone histomorphometry. J Nucl Med. 2001;42:1091–100.

    CAS  PubMed  Google Scholar 

  40. Piert M, Zittel TT, Jahn M, et al. Increased sensitivity in detection of a porcine high-turnover osteopenia after total gastrectomy by dynamic 18F-fluoride ion PET and quantitative CT. J Nucl Med. 2003;44:117–24.

    PubMed  Google Scholar 

  41. Schiepers C, Nuyts J, Bormans G, et al. Fluoride kinetics of the axial skeleton measured in vivo with fluorine-18-fluoride PET. J Nucl Med. 1997;38:1970–6.

    CAS  PubMed  Google Scholar 

  42. Sörensen J, Ullmark G. PET scanning for evaluation of bone metabolism. Acta Orthop. 2009;80:738–9.

    Article  Google Scholar 

  43. Ullmark G, Sörensen J, Nilsson O. Bone healing of severe acetabular defects after revision arthroplasty. Acta Orthop. 2009;80:179–83. doi:10.3109/17453670902947416.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. J Nucl Med. 2010;51:1826–9. doi:10.2967/jnumed.110.077933.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Foldager CB, Bendtsen M, Bünger C. PET scanning for evaluation of bone metabolism. Acta Orthop. 2009;80:737–8. doi:10.3109/17453670903487040; author reply 738–9.

    Article  PubMed  Google Scholar 

  46. Derlin T, Richter U, Bannas P, et al. Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. J Nucl Med. 2010;51:862–5. doi:10.2967/jnumed.110.076471.

    Article  PubMed  Google Scholar 

  47. Derlin T, Wisotzki C, Richter U, et al. In vivo imaging of mineral deposition in carotid plaque using 18F-sodium fluoride PET/CT: correlation with atherogenic risk factors. J Nucl Med. 2011;52:362–8. doi:10.2967/jnumed.110.081208.

    Article  PubMed  Google Scholar 

  48. Aikawa E, Nahrendorf M, Figueiredo J-L, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841–50. doi:10.1161/CIRCULATIONAHA.107.732867.

    Article  CAS  PubMed  Google Scholar 

  49. Bobryshev YV, Killingsworth MC, Huynh TG, et al. Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin? Basic Res Cardiol. 2006;102:133–43. doi:10.1007/s00395-006-0637-9.

    Article  PubMed  Google Scholar 

  50. Golub EE. Biomineralization and matrix vesicles in biology and pathology. Semin Immunopathol. 2010;33:409–17. doi:10.1007/s00281-010-0230-z.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Proudfoot D, Skepper JN, Hegyi L, et al. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 2000;87:1055–62.

    Article  CAS  PubMed  Google Scholar 

  52. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation. 2008;117:2938–48. doi:10.1161/CIRCULATIONAHA.107.743161.

    Article  PubMed  Google Scholar 

  53. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res. 2011;109:697–711. doi:10.1161/CIRCRESAHA.110.234914.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Irkle A, Bird JL, Dweck MR, et al. 18F-NaF – a specific marker for vascular calcification in atherosclerosis. Paper presented at the American Heart Association Scientific Sessions, Dallas, 2013 p. 1–2.

    Google Scholar 

  55. Hyafil F, Messika-Zeitoun D, Burg S, et al. Detection of 18Fluoride sodium accumulation by positron emission tomography in calcified stenotic aortic valves. Am J Cardiol. 2012;109:1194–6. doi:10.1016/j.amjcard.2011.11.060.

    Article  PubMed  Google Scholar 

  56. Fayad ZA, Mani V, Woodward M, et al. Rationale and design of dal-PLAQUE: a study assessing efficacy and safety of dalcetrapib on progression or regression of atherosclerosis using magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Am Heart J. 2011;162:214–21.e2. doi:10.1016/j.ahj.2011.05.006.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Potter K, Lenzo N, Eikelboom JW, 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. 2009;27:259–65. doi:10.1159/000199463.

    Article  CAS  PubMed  Google Scholar 

  58. Tahara N, Kai H, Ishibashi M, et al. Simvastatin attenuates plaque inflammation. J Am Coll Cardiol. 2006;48:1825–31. doi:10.1016/j.jacc.2006.03.069.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge the work of our group’s collaborators in Cambridge University (Dr Anthony Davenport and Agnese Irkle) and thank them for sharing the data on the pharmacodynamics of 18F-NaF binding in calcified vascular tissue.

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Authors and Affiliations

  1. British Heart Foundation Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK

    Alex Thomas Vesey, Marc Richard Dweck MD & David Ernest Newby MD

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  1. Alex Thomas Vesey
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  2. Marc Richard Dweck MD
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  3. David Ernest Newby MD
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Correspondence to Alex Thomas Vesey .

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Editors and Affiliations

  1. Cardiovascular Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Elena Aikawa

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Vesey, A.T., Dweck, M.R., Newby, D.E. (2015). PET/CT Imaging of Inflammation and Calcification in CAVD: Clinical Studies. In: Aikawa, E. (eds) Cardiovascular Imaging. Springer, Cham. https://doi.org/10.1007/978-3-319-09268-3_10

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  • DOI: https://doi.org/10.1007/978-3-319-09268-3_10

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