Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89 Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall.

Autor: Lobatto ME; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.; Department of Radiology , Spaarne Gasthuis , 2035 RC Haarlem , The Netherlands., Binderup T; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging , Rigshospitalet & University of Copenhagen , 2100 Copenhagen , Denmark., Robson PM; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Giesen LFP; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Calcagno C; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Witjes J; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Fay F; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.; Institut Galien Paris Sud UMR 8612, Faculté de Pharmacie, CNRS, Univ. Paris-Sud Université Paris-Saclay , 92290 Châtenay-Malabry , France., Baxter S; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Wessel CH; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Eldib M; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Bini J; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Carlin SD; Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States., Stroes ESG; Department of Vascular Medicine , Academic Medical Center , 1105 AZ Amsterdam , The Netherlands., Storm G; Department of Targeted Therapeutics, MIRA Institute , University of Twente , 7522 NB Enschede , The Netherlands.; Utrecht Institute for Pharmaceutical Sciences , Utrecht University , 3512 JE Utrecht , The Netherlands., Kjaer A; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging , Rigshospitalet & University of Copenhagen , 2100 Copenhagen , Denmark., Lewis JS; Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.; Program in Molecular Pharmacology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States., Reiner T; Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.; Chemical Biology Program , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States., Fayad ZA; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Mulder WJM; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.; Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems , Eindhoven University of Technology , 5612 AZ Eindhoven , The Netherlands.; Department of Oncological Sciences , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States., Pérez-Medina C; Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.; Centro Nacional de Investigaciones Cardiovasculares Carlos III , 28029 Madrid , Spain.
Jazyk: angličtina
Zdroj: Bioconjugate chemistry [Bioconjug Chem] 2020 Feb 19; Vol. 31 (2), pp. 360-368. Date of Electronic Publication: 2019 Jun 07.
DOI: 10.1021/acs.bioconjchem.9b00256
Abstrakt: Nanotherapy has recently emerged as an experimental treatment option for atherosclerosis. To fulfill its promise, robust noninvasive imaging approaches for subject selection and treatment evaluation are warranted. To that end, we present here a positron emission tomography (PET)-based method for quantification of liposomal nanoparticle uptake in the atherosclerotic vessel wall. We evaluated a modular procedure to label liposomal nanoparticles with the radioisotope zirconium-89 ( 89 Zr). Their biodistribution and vessel wall targeting in a rabbit atherosclerosis model was evaluated up to 15 days after intravenous injection by PET/computed tomography (CT) and PET/magnetic resonance imaging (PET/MRI). Vascular permeability was assessed in vivo using three-dimensional dynamic contrast-enhanced MRI (3D DCE-MRI) and ex vivo using near-infrared fluorescence (NIRF) imaging. The 89 Zr-radiolabeled liposomes displayed a biodistribution pattern typical of long-circulating nanoparticles. Importantly, they markedly accumulated in atherosclerotic lesions in the abdominal aorta, as evident on PET/MRI and confirmed by autoradiography, and this uptake moderately correlated with vascular permeability. The method presented herein facilitates the development of nanotherapy for atherosclerotic disease as it provides a tool to screen for nanoparticle targeting in individual subjects' plaques.
Databáze: MEDLINE