Multimodal positron emission tomography imaging to quantify uptake of (89)Zr-labeled liposomes in the atherosclerotic vessel wall Journal Article


Authors: Lobatto, M. E.; Binderup, T.; Robson, P. M.; Giesen, L. F. P.; Calcagno, C.; Witjes, J.; Fay, F.; Baxter, S.; Wessel, C. H.; Eldib, M.; Bini, J.; Carlin, S. D.; Stroes, E. S. G.; Storm, G.; Kjaer, A.; Lewis, J. S.; Reiner, T.; Fayad, Z. A.; Mulder, W. J. M.; Pérez-Medina, C.
Article Title: Multimodal positron emission tomography imaging to quantify uptake of (89)Zr-labeled liposomes in the atherosclerotic vessel wall
Abstract: 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 (89Zr). 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 89Zr-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. Copyright © 2019 American Chemical Society.
Journal Title: Bioconjugate Chemistry
Volume: 31
Issue: 2
ISSN: 1043-1802
Publisher: American Chemical Society  
Date Published: 2020-02-19
Start Page: 360
End Page: 368
Language: English
DOI: 10.1021/acs.bioconjchem.9b00256
PUBMED: 31095372
PROVIDER: scopus
PMCID: PMC7460274
DOI/URL:
Notes: Article -- Export Date: 1 April 2020 -- Source: Scopus
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  1. Jason S Lewis
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  2. Sean Denis Carlin
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  3. Thomas Reiner
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