Elsevier

Journal of Nuclear Cardiology

Volume 5, Issue 6, November–December 1998, Pages 551-557
Journal of Nuclear Cardiology

Original article
Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells

https://doi.org/10.1016/S1071-3581(98)90108-8Get rights and content

Abstract

Background. Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques.

Methods. The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 μg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48 , and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining.

Results. Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed.

Conclusion. This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.

References (41)

  • V Fuster et al.

    The pathogenesis of coronary artery disease

    N Engl J Med

    (1991)
  • R Ross

    The pathogenesis of atherosclerosis- and update

    N Engl J Med

    (1986)
  • J Narula et al.

    Monoclonal antibodies for the detection of atherosclerotic lesions

  • AC Van der Wall et al.

    Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of dominant plaque morphology

    Circulation

    (1994)
  • EW Rainess et al.

    Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis

    Br Heart J

    (1993)
  • O Korcher et al.

    Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening: biochemical and morphologic studies

    Lab Invest

    (1991)
  • HM Loree et al.

    Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels

    Circ Res

    (1992)
  • A Matsumoto et al.

    Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions

  • SM Moerlein et al.

    Metabolic imaging with 68Ga and 111In-labeled LDL

    J Nucl Med

    (1991)
  • RS Lees et al.

    External imaging of human atherosclerosis

    J Nucl Med

    (1983)

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