Molecular Imaging of Apoptosis in Atherosclerosis by Targeting Cell Membrane Phospholipid Asymmetry.

Autor:	Chaudhry F; Icahn School of Medicine at Mount Sinai, New York, New York; Wayne State University School of Medicine, Detroit, Michigan., Kawai H; Icahn School of Medicine at Mount Sinai, New York, New York; Department of Cardiology, Fujita Health University, Toyoake, Aichi, Japan., Johnson KW; Icahn School of Medicine at Mount Sinai, New York, New York., Narula N; New York University Langone Medical Center, New York, New York., Shekhar A; Icahn School of Medicine at Mount Sinai, New York, New York., Chaudhry F; Icahn School of Medicine at Mount Sinai, New York, New York., Nakahara T; Icahn School of Medicine at Mount Sinai, New York, New York., Tanimoto T; Icahn School of Medicine at Mount Sinai, New York, New York., Kim D; Icahn School of Medicine at Mount Sinai, New York, New York., Adapoe MKMY; Icahn School of Medicine at Mount Sinai, New York, New York., Blankenberg FG; Lucile Salter Packard Children's Hospital, Stanford, California., Mattis JA; Molecular Targeting Technologies, Inc., West Chester, Pennsylvania., Pak KY; Molecular Targeting Technologies, Inc., West Chester, Pennsylvania., Levy PD; Wayne State University School of Medicine, Detroit, Michigan., Ozaki Y; Department of Cardiology, Fujita Health University, Toyoake, Aichi, Japan., Arbustini E; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy., Strauss HW; Icahn School of Medicine at Mount Sinai, New York, New York; Memorial Sloan Kettering Cancer Center, New York, New York., Petrov A; Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: artiom.petrov@mssm.edu., Fuster V; Icahn School of Medicine at Mount Sinai, New York, New York; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Narula J; Icahn School of Medicine at Mount Sinai, New York, New York.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2020 Oct 20; Vol. 76 (16), pp. 1862-1874.
DOI:	10.1016/j.jacc.2020.08.047
Abstrakt:	Background: Apoptosis in atherosclerotic lesions contributes to plaque vulnerability by lipid core enlargement and fibrous cap attenuation. Apoptosis is associated with exteriorization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell membrane. Although PS-avid radiolabeled annexin-V has been employed for molecular imaging of high-risk plaques, PE-targeted imaging in atherosclerosis has not been studied. Objectives: This study sought to evaluate the feasibility of molecular imaging with PE-avid radiolabeled duramycin in experimental atherosclerotic lesions in a rabbit model and compare duramycin targeting with radiolabeled annexin-V. Methods: Of the 27 rabbits, 21 were fed high-cholesterol, high-fat diet for 16 weeks. Nine of the 21 rabbits received 99m Tc-duramycin (test group), 6 received 99m Tc-linear duramycin (duramycin without PE-binding capability, negative radiotracer control group), and 6 received 99m Tc-annexin-V for radionuclide imaging. The remaining normal chow-fed 6 animals (disease control group) received 99m Tc-duramycin. In vivo microSPECT/microCT imaging was performed, and the aortas were explanted for ex vivo imaging and for histological characterization of atherosclerosis. Results: A significantly higher duramycin uptake was observed in the test group compared with that of disease control and negative radiotracer control animals; duramycin uptake was also significantly higher than the annexin-V uptake. Quantitative duramycin uptake, represented as the square root of percent injected dose per cm (√ID/cm) of abdominal aorta was >2-fold higher in atherosclerotic lesions in test group (0.08 ± 0.01%) than in comparable regions of disease control animals (0.039 ± 0.0061%, p = 3.70·10 -8 ). Mean annexin uptake (0.060 ± 0.010%) was significantly lower than duramycin (p = 0.001). Duramycin uptake corresponded to the lesion severity and macrophage burden. The radiation burden to the kidneys was substantially lower with duramycin (0.49% ID/g) than annexin (5.48% ID/g; p = 4.00·10 -4 ). Conclusions: Radiolabeled duramycin localizes in lipid-rich areas with high concentration of apoptotic macrophages in the experimental atherosclerosis model. Duramycin uptake in atherosclerotic lesions was significantly greater than annexin-V uptake and produced significantly lower radiation burden to nontarget organs. (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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