دورية أكاديمية
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PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody Detects Clinically Relevant Atherothrombosis.

التفاصيل البيبلوغرافية
العنوان: PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody Detects Clinically Relevant Atherothrombosis.
المؤلفون: Senders ML; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands., Que X; Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California., Cho YS; Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California San Diego, La Jolla, California., Yeang C; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California San Diego, La Jolla, California., Groenen H; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Fay F; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Chemistry and Pharmaceutical Science, York College of The City University of New York, New York, New York., Calcagno C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Meerwaldt AE; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Green S; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California San Diego, La Jolla, California., Miu P; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California San Diego, La Jolla, California., Lobatto ME; Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands., Reiner T; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiology, Weill Cornell Medical College, New York, New York., Fayad ZA; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Witztum JL; Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California., Mulder WJM; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands., Pérez-Medina C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: carlos.perez-medina@mountsinai.org., Tsimikas S; Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
المصدر: Journal of the American College of Cardiology [J Am Coll Cardiol] 2018 Jan 23; Vol. 71 (3), pp. 321-335.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Biomedical Country of Publication: United States NLM ID: 8301365 Publication Model: Print Cited Medium: Internet ISSN: 1558-3597 (Electronic) Linking ISSN: 07351097 NLM ISO Abbreviation: J Am Coll Cardiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [New York, N.Y.] : Elsevier Biomedical, [c1983-
مواضيع طبية MeSH: Acetaldehyde*/metabolism , Malondialdehyde*/metabolism, Atherosclerosis/*diagnostic imaging , Magnetic Resonance Imaging/*methods , Positron-Emission Tomography/*methods , Thrombosis/*diagnostic imaging, Animals ; Atherosclerosis/metabolism ; Epitopes/metabolism ; Humans ; Mice ; Mice, Knockout ; Rabbits ; Thrombosis/metabolism ; Tissue Distribution/physiology
مستخلص: Background: Oxidation-specific epitopes (OSEs) are proinflammatory, and elevated levels in plasma predict cardiovascular events.
Objectives: The purpose of this study was to develop novel positron emission tomography (PET) probes to noninvasively image OSE-rich lesions.
Methods: An antigen-binding fragment (Fab) antibody library was constructed from human fetal cord blood. After multiple rounds of screening against malondialdehyde-acetaldehyde (MAA) epitopes, the Fab LA25 containing minimal nontemplated insertions in the CDR3 region was identified and characterized. In mice, pharmacokinetics, biodistribution, and plaque specificity studies were performed with Zirconium-89 ( 89 Zr)-labeled LA25. In rabbits, 89 Zr-LA25 was used in combination with an integrated clinical PET/magnetic resonance (MR) system. 18 F-fluorodeoxyglucose PET and dynamic contrast-enhanced MR imaging were used to evaluate vessel wall inflammation and plaque neovascularization, respectively. Extensive ex vivo validation was carried out through a combination of gamma counting, near infrared fluorescence, autoradiography, immunohistochemistry, and immunofluorescence.
Results: LA25 bound specifically to MAA epitopes in advanced and ruptured human atherosclerotic plaques with accompanying thrombi and in debris from distal protection devices. PET/MR imaging 24 h after injection of 89 Zr-LA25 showed increased uptake in the abdominal aorta of atherosclerotic rabbits compared with nonatherosclerotic control rabbits, confirmed by ex vivo gamma counting and autoradiography. 18 F-fluorodeoxyglucose PET, dynamic contrast-enhanced MR imaging, and near-infrared fluorescence signals were also significantly higher in atherosclerotic rabbit aortas compared with control aortas. Enhanced liver uptake was also noted in atherosclerotic animals, confirmed by the presence of MAA epitopes by immunostaining.
Conclusions: 89 Zr-LA25 is a novel PET radiotracer that may allow noninvasive phenotyping of high-risk OSE-rich lesions.
(Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
التعليقات: Comment in: J Am Coll Cardiol. 2018 Jan 23;71(3):336-338. (PMID: 29348026)
Comment in: Nat Rev Cardiol. 2018 Mar;15(3):135. (PMID: 29388566)
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معلومات مُعتمدة: P01 HL088093 United States HL NHLBI NIH HHS; R01 HL125703 United States HL NHLBI NIH HHS; R35 HL135737 United States HL NHLBI NIH HHS; R01 HL106579 United States HL NHLBI NIH HHS; P01 HL136275 United States HL NHLBI NIH HHS; P01 HL131478 United States HL NHLBI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 HL128550 United States HL NHLBI NIH HHS; R01 HL078610 United States HL NHLBI NIH HHS; R01 HL136098 United States HL NHLBI NIH HHS; R01 HL119828 United States HL NHLBI NIH HHS; P01 HL055798 United States HL NHLBI NIH HHS; R01 EB009638 United States EB NIBIB NIH HHS
فهرسة مساهمة: Keywords: PET/MR imaging; atherosclerosis; natural antibodies; oxidation-specific epitopes
المشرفين على المادة: 0 (Epitopes)
4Y8F71G49Q (Malondialdehyde)
GO1N1ZPR3B (Acetaldehyde)
تواريخ الأحداث: Date Created: 20180120 Date Completed: 20190710 Latest Revision: 20220408
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5995462
DOI: 10.1016/j.jacc.2017.11.036
PMID: 29348025
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-3597
DOI:10.1016/j.jacc.2017.11.036