دورية أكاديمية
أعرض في EDS

In Vivo PET Imaging of HDL in Multiple Atherosclerosis Models.

التفاصيل البيبلوغرافية
العنوان: In Vivo PET Imaging of HDL in Multiple Atherosclerosis Models.
المؤلفون: Pérez-Medina C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Binderup T; Clinical Physiology, Nuclear Medicine, PET and Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark., Lobatto ME; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands., Tang J; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Calcagno C; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Giesen L; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Wessel CH; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Witjes J; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Ishino S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Baxter S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Zhao Y; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Ramachandran S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Eldib M; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Sánchez-Gaytán BL; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Robson PM; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Bini J; School of Engineering & Applied Science, Yale University, New Haven, Connecticut., Granada JF; CRF Skirball Center for Innovation, The Cardiovascular Research Foundation, Orangeburg, New York., Fish KM; Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York., Stroes ES; Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands., Duivenvoorden R; Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands., Tsimikas S; Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California., Lewis JS; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Reiner T; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Fuster V; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Kjær A; Clinical Physiology, Nuclear Medicine and PET, University of Copenhagen, Copenhagen, Denmark., Fisher EA; Leon H. Charney Division of Cardiology and Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, New York, New York., Fayad ZA; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Mulder WJ; 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. Electronic address: willem.mulder@mssm.edu.
المصدر: JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2016 Aug; Vol. 9 (8), pp. 950-61. Date of Electronic Publication: 2016 May 25.
نوع المنشور: Journal Article; Validation Study
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 101467978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1876-7591 (Electronic) Linking ISSN: 18767591 NLM ISO Abbreviation: JACC Cardiovasc Imaging Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Elsevier
مواضيع طبية MeSH: Magnetic Resonance Imaging* , Plaque, Atherosclerotic* , Positron Emission Tomography Computed Tomography*, Aorta/*diagnostic imaging , Aortic Diseases/*diagnostic imaging , Atherosclerosis/*diagnostic imaging , Lipoproteins, HDL/*administration & dosage , Molecular Imaging/*methods , Radiopharmaceuticals/*administration & dosage , Zirconium/*administration & dosage, Animals ; Aorta/metabolism ; Aorta/pathology ; Aortic Diseases/genetics ; Aortic Diseases/metabolism ; Aortic Diseases/pathology ; Apolipoproteins E/deficiency ; Apolipoproteins E/genetics ; Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Autoradiography ; Disease Models, Animal ; Female ; Flow Cytometry ; Lipoproteins, HDL/pharmacokinetics ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Optical Imaging ; Predictive Value of Tests ; Rabbits ; Radioisotopes ; Radiopharmaceuticals/pharmacokinetics ; Reproducibility of Results ; Tissue Distribution ; Zirconium/pharmacokinetics
مستخلص: Objectives: The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities.
Background: HDL is a natural nanoparticle that interacts with atherosclerotic plaque macrophages to facilitate reverse cholesterol transport. HDL-cholesterol concentration in blood is inversely associated with risk of coronary heart disease and remains one of the strongest independent predictors of incident cardiovascular events.
Methods: Discoidal HDL nanoparticles were prepared by reconstitution of its components apolipoprotein A-I (apo A-I) and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine. For radiolabeling with zirconium-89 ((89)Zr), the chelator deferoxamine B was introduced by conjugation to apo A-I or as a phospholipid-chelator (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-deferoxamine B). Biodistribution and plaque targeting of radiolabeled HDL were studied in established murine, rabbit, and porcine atherosclerosis models by using PET combined with computed tomography (PET/CT) imaging or PET combined with magnetic resonance imaging. Ex vivo validation was conducted by radioactivity counting, autoradiography, and near-infrared fluorescence imaging. Flow cytometric assessment of cellular specificity in different tissues was performed in the murine model.
Results: We observed distinct pharmacokinetic profiles for the two (89)Zr-HDL nanoparticles. Both apo A-I- and phospholipid-labeled HDL mainly accumulated in the kidneys, liver, and spleen, with some marked quantitative differences in radioactivity uptake values. Radioactivity concentrations in rabbit atherosclerotic aortas were 3- to 4-fold higher than in control animals at 5 days' post-injection for both (89)Zr-HDL nanoparticles. In the porcine model, increased accumulation of radioactivity was observed in lesions by using in vivo PET imaging. Irrespective of the radiolabel's location, HDL nanoparticles were able to preferentially target plaque macrophages and monocytes.
Conclusions: (89)Zr labeling of HDL allows study of its in vivo behavior by using noninvasive PET imaging, including visualization of its accumulation in advanced atherosclerotic lesions. The different labeling strategies provide insight on the pharmacokinetics and biodistribution of HDL's main components (i.e., phospholipids, apo A-I).
(Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
التعليقات: Comment in: JACC Cardiovasc Imaging. 2016 Aug;9(8):962-3. (PMID: 27236525)
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معلومات مُعتمدة: R01 HL125703 United States HL NHLBI NIH HHS; HHSN268201000045C United States HL NHLBI NIH HHS; R01 HL071021 United States HL NHLBI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 CA155432 United States CA NCI NIH HHS; K25 EB016673 United States EB NIBIB NIH HHS; R01 EB009638 United States EB NIBIB NIH HHS; R01 HL118440 United States HL NHLBI NIH HHS; P01 HL092969 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: PET/CT; PET/MRI; atherosclerosis; high-density lipoprotein; zirconium-89
المشرفين على المادة: 0 (Apolipoproteins E)
0 (Lipoproteins, HDL)
0 (Radioisotopes)
0 (Radiopharmaceuticals)
C6V6S92N3C (Zirconium)
تواريخ الأحداث: Date Created: 20160530 Date Completed: 20171023 Latest Revision: 20210630
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5589956
DOI: 10.1016/j.jcmg.2016.01.020
PMID: 27236528
قاعدة البيانات: MEDLINE
الوصف
تدمد:1876-7591
DOI:10.1016/j.jcmg.2016.01.020