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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1998-11

AUTHORS

Ignasi Carrió, Pier Luigi Pieri, Jagat Narula, Lourdes Prat, Pietro Riva, Luciano Pedrini, Enzo Pretolani, Guillermo Caruso, Graciella Sarti, Montserrat Estorch, Lluis Berná, Vicens Riambau, Xavier Matias-Guiu, Chris Pak, Charles Ditlow, Francis Chen, Ban An Khaw

ABSTRACT

BackgroundTargeting 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.MethodsThe 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.ResultsUptake 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.ConclusionThis 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. More... »

PAGES

551-557

References to SciGraph publications

  • 1993-12. Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1016/s1071-3581(98)90108-8

    DOI

    http://dx.doi.org/10.1016/s1071-3581(98)90108-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1018656592

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9869476


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        "description": "BackgroundTargeting 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\u2032)2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques.MethodsThe 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 \u03bcg) 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.ResultsUptake 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.ConclusionThis 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.", 
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