Targeting Atherosclerotic Plaques

  • Ban-An Khaw


Clinical imaging of atherosclerotic plaques is based on anatomical demonstration of the narrowing of the involved artery (1). Angioscopy (2) and intravascular ultrasound (3) can demonstrate the precise location of the lesions, the extent of luminal narrowing and plaque thickening. However, both methods are invasive and cannot provide the composition or the metabolic status of the atherosclerotic lesion (4). Plaques rich in macrophages and foam cells may denote high risk of plaque rapture (5) whereas fibrous plaques may denote slowly emergent lesions. Lesions rich in actively proliferating smooth muscle cells may be an indication of accelerated luminal diameter reduction (6). Other targets that might have potential applications may be associated with neoantigens that are expressed due to microvascular injury inherent in atherogenesis. Therefore, targeting macrophage, foam cell hyper-accumulation or hyperactivity intravascularly, neoexpression or hyperexpression of various vascular adhesion molecules, or the metabolites that may be incorporated into the cellular components of the atherosclerotic lesions may provide novel and specific diagnostic and therapeutic applications.


Smooth Muscle Cell Atherosclerotic Lesion Proliferate Smooth Muscle Cell Carotid Lesion Endothelial Denudation 
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  1. 1.
    Sones FM, Shirley EK. Cine coronary arteriography. Mod Concepts Cardiovascl Dis 1962; 31: 735–751.Google Scholar
  2. 2.
    Sherman CT, Litvack F, Grundfest W, et al. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med. 1986; 315: 913–919.CrossRefGoogle Scholar
  3. 3.
    Tardif JC, Pandian NG. Intravascular ultrasound imaging in peripheral arterial and coronary artery disease. Curr Opin Cardiol. 1994; 9: 627–633.CrossRefGoogle Scholar
  4. 4.
    Khaw BA, Carrio I, Pieri PL, Narula J. Radionuclide imaging of the synthetic smooth muscle cell phenotype in experimental atheroscelrotic lesions. Trends in Cardiovascular Med. 1996; 7: 226–232.CrossRefGoogle Scholar
  5. 5.
    Falk, E, Shah P, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657671.Google Scholar
  6. 6.
    Holmes DR Jr, Vliestra RE, Smith HC, et al. Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from PTCA registry of the HHLBI. Am J Cardiol. 1984; 53: 77C - 81C.CrossRefGoogle Scholar
  7. 7.
    Narula, J, Ditlaow C, Chen F, Khaw BA. “Monoclonal antibodies for the detection of atherosclerotic lesions.” In: Monoclonal antibodies in cardiovascular diseases. Khaw BA, Narula J, Strauss HW, ed. Lea and Febiger, Philadelphia. 1994; pp 206215.Google Scholar
  8. 8.
    DiCorleto PE, Chisolm GM. Participation of the endothelium in the development of the atherosclerotic plaque. Prog Lipid Res 1986; 25: 365–374.CrossRefGoogle Scholar
  9. 9.
    Parthasarthy S, Steinbrecher UP, Barnett J, Witztum JL, Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci USA 1985; 82: 3000–3004.CrossRefGoogle Scholar
  10. 10.
    Goldstein JL, Ho YK, Basu SK, Brown MS,. Binding site on macrophages that mediates uptake and degredation oof acetylated low density lipoprotein, producing massive choletsterol deposition. Proc Natl Acad Sci UAS 1979; 76: 333–337.CrossRefGoogle Scholar
  11. 11.
    Roberts AB, Lee AM, Lees RS, Strauss HW, Fallon JT, Taveras J, Kopiwoda S. Selective accumulation of low dsensity lipoproteins in damaged arterial wall. J Lipid Res. 1983; 24: 1160–1167.Google Scholar
  12. 12.
    Davis HH, Siegel BA, Joist JH, Heaton WA, Mathias CJ, Sherman LA, Welch MJ. Scintigraphic detection of atherosclerotic lesions and venous thrombi in man by In-111 labeled autologous platelets. Lancet 1978; 1: 1185–1187.CrossRefGoogle Scholar
  13. 13.
    Narula J, Petrov A, Bianchi C, Ditlow CC, Dilley J, Pieslak I, Chen FW, Torchilin VP, Khaw BA. Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 antibody specific for the proliferating smooth muscle cells of human atheroma: Imaging with conventional antibody and image enhancement with negative charge-modified antibody. Circulation 1995; 92: 474–484.CrossRefGoogle Scholar
  14. 14.
    Elmaleh DR, Narula J, Babich JW, Petrov A, Fischman AJ, Khaw BA, Rapaport E, Zamecnik PC. Rapid noninvasive detection of expertimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates. Proc Nat Acad Sci. USA. 1998; 95: 691–695.CrossRefGoogle Scholar
  15. 15.
    Moerlein SM, Daugherty A, Sobel BE, Welch MJ. Metabolic imaging with 68Ga and “’In-labeled LDL. J Nucl Med 1991; 32: 300–307.Google Scholar
  16. 16.
    Lees RS, Lees AM, Strauss HW. External imaging of human atherosclerosis. J Nucl Med 1983; 24: 154–156.Google Scholar
  17. 17.
    Lees AM, Lees RS, Schoen FJ, Issachsohn JL, Fischman AJ, McKusick KA, Strauss HW. Imaging human atherosclerosis with Tc-99m-labeled LDL. Atherosclerosis 1988; 8: 461–470.Google Scholar
  18. 18.
    Virgolino I, Muller F, Fitscha P, Chiba P, Sinzinger H. Radiolabeling autologous monocytes with “’In oxine for reinjection in patients with atherosclerosis. Prog Clin Biol Res 1989; 355: 271–280.Google Scholar
  19. 19.
    Fischman AJ, Rubin RH, Khaw BA, Kramer PB, Wilkinson R, Ahmad M, Needelman M, Locke E, Nossiff ND, Strauss HW. Radionuclide imaging of experimental atherosclerosis with non-specific polyclonal immunoglobulin G. J Nucl Med. 1989; 29: 1095–1100.Google Scholar
  20. 20.
    Fischman AJ, Rubin RH, Delvecchio A, Ahmed M, Khaw BA, Callahan RJ, LaMuraglia GM, Strauss HW. Imaging of atheromatous lesions in the iliac and femoral vessels: preliminary experience with indium-111-IgG in human subjects. J Nucl Med. 1989; 30 (5): 817.Google Scholar
  21. 21.
    Watanabe T, Hirata M, Yoshikawa Y, Nagafuchi Y, Toyoshima H, Watanabe T. Role of macrophages in atherosclerosis. Sequential observations of cholesterlinduced rabbit aortic lesion by the immunoperoxidasse technique using monoclonal antimacrophage antibody. Lab Invest 1985; 53 (1): 80–90Google Scholar
  22. 22.
    Agel NM, Ball RY, Waldmann H, Mitchinson MJ. Identification of macrophages and smooth muscle cells in human atherosclerosis using monoclonal antibodies. J Pathol 1985; 146: 197–204.CrossRefGoogle Scholar
  23. 23.
    Gown AM, Tsukada T, Ross R. Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am L Pathol 1986; 125: 1910297.Google Scholar
  24. 24.
    Miller DD, Boulet Ai, Tio PO, Garcia OJ, Guy DM, McEver RP, Palmer JC, Pak KY, Neblock DS, Berger HJ. In vivo 99m Tc S12 antibody imaging of platelet alpha granules in rabbit endothelial neointimal proliferation after angioplasty. Circulation 1991; 83: 224–236.CrossRefGoogle Scholar
  25. 25.
    Mettinger KL, Ericson K, Larson S, Casseborn S. Detection of atherosclerotic plaques in carotid arteries by the use of 123I fibrinogen. Lancet 1978; 1: 242–244.CrossRefGoogle Scholar
  26. 26.
    Minar E, Ehringer H, Dudczak R, Schofl R, Jung M, Koppensteiner R, Ahmadi R, Kreschmer G. ii In-labeled platelet scintigraphy in carotid atherosclerosis. Stroke 1989; 20: 27–33.CrossRefGoogle Scholar
  27. 27.
    Harrison DC, Calenoff E, Chen F, Parmley W, Khaw BA, Ross R. Plaque-Associated Immune Reactivity as a Tool for the Diagnosis and Treatment of Atherosclerosis. Proceedings of the American Clinical and Climabiological Association. Trans Am Clin Climatol Assoc. 1992; 103: 210–217.Google Scholar
  28. 28.
    Khaw BA, Calenoff E, Chen F, O’Donnell SM, Nossiff ND, Strauss HW. Localization of Experimental Atherosclerotic Lesion with Monoclonal Antibody Z2D3. J Nucl Med. 1991; 32 (5): 1005.Google Scholar
  29. 29.
    Sharifi J, Khawli LA, Hornick JL, Epstein AL. Improving monoclonal antibody pharmacokinetics via chemical modification. Q J Nucl Med 1998 Dec; 42 (4): 242–9Google Scholar
  30. 30.
    Colcher D, Pavlinkova G, Beresford G, Booth BJ, Choudhury A, Batra SK. Pharmacokinetics and biodistribution of genetically-engineered antibodies. Q J Nucl Med 1998 Dec; 42 (4): 225–41Google Scholar
  31. 31.
    Khawli LA, Glasky MS, Alauddin MM, Epstein AL. Improved tumor localization and radioimaging with chemically modified monoclonal antibodies. Cancer Biother Radiopharm 1996; 11: 203–15.CrossRefGoogle Scholar
  32. 32.
    Khaw BA, Klibanov A, O’Donnell SM, Siato T, Nossiff N, Slinkin MA, Newell JB, Strauss HW, Torchilin VP. Gamma imaging with negatively charge-modified monoclonal antibody; Modification with synthetic polymers. J Nucl Med. 1991; 32: 1742–1751.Google Scholar
  33. 33.
    Narula J, Petrov A, Ditlow C, Pak KY, Chen FW, Khaw BA. Maximizing radiotracer delivery for scintigraphic localization of experimental atherosclerotic lesions with high-dose negative-charge-modified Z2D3 antibody. J Nucl Cardiol; 1997; 4: 226–233.CrossRefGoogle Scholar
  34. 34.
    Johnson LL, Schofield LM, Verdesca SA, Sharaf BL, Jones RM, Virmani R, Khaw BA. In-vivo uptake of radiolabeled antibody to proliferating smooth muscle cells in a swine model of coronary stent restenosis. J Nucl Med. 2000; 41: 1535–1540.Google Scholar
  35. 35.
    Carri6 I, Pieri PL, Narula J, Prat L, Riva P, Pedrini L, Pretolani E, Caruso G, Sarti G, Estorch M, Berna L, Riambau V, Matias-Guiu X, Pak C, Ditlow C, Chen F, Khaw BA. Noninvasive localization of human atherosclerotic lesions with In-111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells. J Nucl Cardiol 1998; 5: 551–557.CrossRefGoogle Scholar
  36. 36.
    Pintor J, Miras-Portugal MT. Diadenosine polyphosphates (ApxA) as new neurotransmitters. Drug Dev Res 1993; 28: 259–262.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ban-An Khaw
    • 1
  1. 1.Bouve College of Health Sciences, School of Pharmacy, Department of Pharmaceutical SciencesNortheastern UniversityBostonUSA

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