Current Cardiology Reports

, Volume 10, Issue 2, pp 121–127 | Cite as

Molecular imaging of atherosclerosis



Techniques are being developed for clinical molecular imaging of atherosclerosis to identify and characterize vulnerable plaques in each vascular territory. Molecular imaging encompasses multiple imaging modalities that depict cellular and subcellular processes. Molecular imaging can provide a “virtual histology” noninvasively about atherosclerotic disease, characterizing vascular lesions with markers of inflammation, angiogenesis, lipid metabolism, and more.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Morawski AM, Winter PM, Crowder KC, et al.: Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 2004, 51:480–486.PubMedCrossRefGoogle Scholar
  2. 2.
    Kukreja N, Garcia-Garcia HM, Serruys PW: Invasive imaging techniques for the assessment of vulnerable plaque. Minerva Cardioangiol 2006, 54:603–617.PubMedGoogle Scholar
  3. 3.
    Dunphy MPS, Schoder H, Strauss HW: Radionuclide techniques for identifying vulnerable plaque. J Nucl Med 2007, 48:1753–1755.PubMedCrossRefGoogle Scholar
  4. 4.
    Lees RS, Lees AM, Strauss HW: External imaging of human atherosclerosis. J Nucl Med 1983, 24:154–156.PubMedGoogle Scholar
  5. 5.
    Fischman AJ, Lees AM, Lees RS, et al.: Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall. Arteriosclerosis 1987, 7:361–366.PubMedGoogle Scholar
  6. 6.
    Shaish A, Keren G, Chouraqui P, et al.: Imaging of aortic atherosclerotic lesions by (125)I-LDL, (125)I-oxidized-LDL, (125)I-HDL and (125)I-BSA. Pathobiology 2001, 69:225–229.PubMedCrossRefGoogle Scholar
  7. 7.
    Tsimikas S: Noninvasive imaging of oxidized low-density lipoprotein in atherosclerotic plaques with tagged oxidation-specific antibodies. Am J Cardiol 2002, 90(10C):22L–27L.PubMedCrossRefGoogle Scholar
  8. 8.
    Narula J, Petrov A, Bianchi C, et al.: Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab’)2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments. Circulation 1995, 92:474–484.PubMedGoogle Scholar
  9. 9.
    Dietrich T, Perlitz C, Licha K, et al.: ED-B fibronectin (ED-B) can be targeted using a novel single chain antibody conjugate and is associated with macrophage accumulation in atherosclerotic lesions. Basic Res Cardiol 2007, 102:298–307.PubMedCrossRefGoogle Scholar
  10. 10.
    Tepe G, Duda SH, Meding J, et al.: Tc-99m-labeled endothelin derivative for imaging of experimentally induced atherosclerosis. Atherosclerosis 2001, 157:383–392.PubMedCrossRefGoogle Scholar
  11. 11.
    Johnstrom P, Rudd JH, Richards HK, et al.: Imaging endothelin ET(B) receptors using [18F]-BQ3020: in vitro characterization and positron emission tomography (microPET). Exp Biol Med 2006, 231:736–740.Google Scholar
  12. 12.
    Fischman AJ, Rubin RH, Khaw BA, et al.: Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G. J Nucl Med 1989, 30:1095–1100.PubMedGoogle Scholar
  13. 13.
    Ohtsuki K, Hayase M, Akashi K, et al.: Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study. Circulation 2001, 104:203–208.PubMedGoogle Scholar
  14. 14.
    Vallabhajosula S, Machac J, Knesaurek K, et al.: Imaging atherosclerotic macrophage density by positron emission tomography using F-18 fluorodeoxyglucose (FDG) [abstract]. J Nucl Med 1996, 37(Suppl):38P.Google Scholar
  15. 15.
    Dunphy MP, Freiman A, Larson SM, Strauss HW: Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 2005, 46:1278–1284.PubMedGoogle Scholar
  16. 16.
    Zhao Y, Kuge Y, Zhao S, et al.: Comparison of (99m)Tcannexin A5 with (18)F-FDG for the detection of atherosclerosis in ApoE-/-mice. Eur J Nucl Med Mol Imaging 2007, 34:1747–1755.PubMedCrossRefGoogle Scholar
  17. 17.
    Schafers M, Riemann B, Kopka K, et al.: Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation 2004, 109:2554–2559.PubMedCrossRefGoogle Scholar
  18. 18.
    Kolodgie FD, Petrov A, Virmani R, et al.: Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 2003, 108:3134–3139.PubMedCrossRefGoogle Scholar
  19. 19.
    Hartung D, Sarai M, Petrov A, et al.: Resolution of apoptosis in atherosclerotic plaque by dietary modification and statin therapy. J Nucl Med 2005, 46:2051–2056.PubMedGoogle Scholar
  20. 20.
    Strauss HW, Mari C, Patt BE, Ghazarossian V: Intravascular radiation detectors for the detection of vulnerable atheroma. J Am Coll Cardiol 2006, 47(8 Suppl):C97–C100.PubMedCrossRefGoogle Scholar
  21. 21.
    Virgolini I, O’Grady J, Lupattelli G, et al.: In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL). Int J Rad Appl Instrum 1992, 19:245–250.Google Scholar
  22. 22.
    Virgolini I, Rauscha F, Lupattelli G, et al.: Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage. Eur J Nucl Med 1991, 18:948–951.PubMedGoogle Scholar
  23. 23.
    Hardoff R, Braegelmann F, Zanzonico P, et al.: External imaging of atherosclerosis in rabbits using an 123I-labeled synthetic peptide fragment. J Clin Pharmacol 1993, 33:1039–1047.PubMedGoogle Scholar
  24. 24.
    Munro JM, van der Walt JD, Munro CS, et al.: An immunohistochemical analysis of human aortic fatty streaks. Hum Pathol 1987, 18:375–380.PubMedCrossRefGoogle Scholar
  25. 25.
    Jonasson L, Holm J, Skalli O, et al.: Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 1986, 6:131–138.PubMedGoogle Scholar
  26. 26.
    Aqel NM, Ball RY, Waldmann H, Mitchinson MJ: Monocytic origin of foam cells in human atherosclerotic plaques. Atherosclerosis 1984, 53:265–271.PubMedCrossRefGoogle Scholar
  27. 27.
    Buono C, Pang H, Uchida Y, et al.: B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice. Circulation 2004, 109:2009–2015.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou X, Robertson AK, Hjerpe C, Hansson GK: Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis. Arterioscler Thromb Vasc Biol 2006, 26:864–870.PubMedCrossRefGoogle Scholar
  29. 29.
    Bobryshev YV, Lord RS: Detection of vascular dendritic cells accumulating calcified deposits in their cytoplasm. Tissue Cell 1998, 30:383–388.PubMedCrossRefGoogle Scholar
  30. 30.
    Yilmaz A, Lochno M, Traeg F, et al.: Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis 2004, 176:101–110.PubMedCrossRefGoogle Scholar
  31. 31.
    Whitman SC, Rateri DL, Szilvassy SJ, et al.: Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice. Arterioscler Thromb Vasc Biol 2004, 24:1049–1054.PubMedCrossRefGoogle Scholar
  32. 32.
    Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998, 392:245–252.PubMedCrossRefGoogle Scholar
  33. 33.
    Bobryshev YV, Lord RS: Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions. Cardiovasc Res 1998, 37:799–810.PubMedCrossRefGoogle Scholar
  34. 34.
    Bobryshev YV, Lord RS: Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis. J Vasc Surg 2002, 35:368–375.PubMedCrossRefGoogle Scholar
  35. 35.
    Stocker R, Keaney JF, Jr: Role of oxidative modifications in atherosclerosis. Physiol Rev 2004, 84:1381–1478.PubMedCrossRefGoogle Scholar
  36. 36.
    Heidenthal AK, Weber PC, Lottspeich F, Hrboticky N: The binding in vitro of modified LDL to the intermediate filament protein vimentin. Biochemical and biophysical research communications. 2000, 267:49–53.PubMedCrossRefGoogle Scholar
  37. 37.
    Kishikawa H, Shimokama T, Watanabe T: Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis. Virchows Arch 1993, 423:433–442.CrossRefGoogle Scholar
  38. 38.
    Stemme S, Holm J, Hansson GK: T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arterioscler Thromb 1992, 12:206–211.PubMedGoogle Scholar
  39. 39.
    Ehlers S, Smith KA: Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med 1991, 173:25–36.PubMedCrossRefGoogle Scholar
  40. 40.
    Stemme S, Rymo L, Hansson GK: Polyclonal origin of T lymphocytes in human atherosclerotic plaques. Lab Invest 1991, 65:654–660.PubMedGoogle Scholar
  41. 41.
    Swanson SJ, Rosenzweig A, Seidman JG, Libby P: Diversity of T-cell antigen receptor V beta gene utilization in advanced human atheroma. Arterioscler Thromb 1994, 14:1210–1214.PubMedGoogle Scholar
  42. 42.
    Caligiuri G, Nicoletti A, Poirier B, Hansson GK: Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest 2002, 109:745–753.PubMedGoogle Scholar
  43. 43.
    Major AS, Fazio S, Linton MF: B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol 2002, 22:1892–1898.PubMedCrossRefGoogle Scholar
  44. 44.
    Galkina E, Kadl A, Sanders J, et al.: Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med 2006, 203:1273–1282.PubMedCrossRefGoogle Scholar
  45. 45.
    Kietselaer BL, Reutelingsperger CP, Heidendal GA, et al.: Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 2004, 350:1472–1473.PubMedCrossRefGoogle Scholar
  46. 46.
    Rudd JH, Warburton EA, Fryer TD, et al.: Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002, 105:2708–2711.PubMedCrossRefGoogle Scholar
  47. 47.
    Breyholz HJ, Wagner S, Levkau B, et al.: A 18F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo. Q J Nucl Med Mol Imaging 2007, 51:24–32.PubMedGoogle Scholar
  48. 48.
    Davies MJ, Richardson PD, Woolf N, et al.: Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993, 69:377–381.PubMedCrossRefGoogle Scholar
  49. 49.
    Burke AP, Kolodgie FD, Farb A, et al.: Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001, 103:934–940.PubMedGoogle Scholar
  50. 50.
    Libby P, Sukhova G, Lee RT, Galis ZS: Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol 1995, 25(Suppl 2):S9–S12.PubMedCrossRefGoogle Scholar
  51. 51.
    Xu Y, Wang L, Buttice G, et al.: Major histocompatibility class II transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by interferon gamma (IFN-gamma). J Biol Chem 2004, 279:41319–41332.PubMedCrossRefGoogle Scholar
  52. 52.
    Dinkelborg LM, Duda SH, Hanke H, et al.: Molecular imaging of atherosclerosis using a technetium-99m-labeled endothelin derivative. J Nucl Med 1998, 39:1819–1822.PubMedGoogle Scholar
  53. 53.
    Bobryshev YV, Babaev VR, Lord RS, Watanabe T: Cell death in atheromatous plaque of the carotid artery occurs through necrosis rather than apoptosis. In Vivo 1997, 11:441–452.PubMedGoogle Scholar
  54. 54.
    Madamanchi NR, Vendrov A, Runge MS: Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 2005, 25:29–38.PubMedCrossRefGoogle Scholar
  55. 55.
    Beer AJ, Haubner R, Sarbia M, et al.: Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 2006, 12:3942–3949.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Memorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations