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

Mark E. Lobatto, Tina Binderup, Philip M. Robson, Luuk F.P. Giesen, Claudia Calcagno, Julia Witjes, Francois Fay, Samantha Baxter, Chang Ho Wessel, Mootaz Eldib, Jason Bini, Sean D. Carlin, Erik S.G. Stroes, Gert Storm, Andreas Kjaer, Jason S. Lewis, Thomas Reiner, Zahi A. Fayad, Willem J.M. Mulder (Corresponding author), Carlos Pérez-Medina (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
JournalBioconjugate Chemistry
DOIs
Publication statusE-pub ahead of print - 16 May 2019

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Positron emission tomography
Liposomes
Positron-Emission Tomography
Nanoparticles
Magnetic resonance imaging
Imaging techniques
Capillary Permeability
Atherosclerosis
Optical Imaging
Abdominal Aorta
Magnetic resonance
Autoradiography
Radioisotopes
Zirconium
Intravenous Injections
Patient Selection
Tomography
Labels
Fluorescence
Magnetic Resonance Imaging

Cite this

Lobatto, Mark E. ; Binderup, Tina ; Robson, Philip M. ; Giesen, Luuk F.P. ; Calcagno, Claudia ; Witjes, Julia ; Fay, Francois ; Baxter, Samantha ; Wessel, Chang Ho ; Eldib, Mootaz ; Bini, Jason ; Carlin, Sean D. ; Stroes, Erik S.G. ; Storm, Gert ; Kjaer, Andreas ; Lewis, Jason S. ; Reiner, Thomas ; Fayad, Zahi A. ; Mulder, Willem J.M. ; Pérez-Medina, Carlos. / Multimodal positron emission tomography imaging to quantify uptake of 89Zr-labeled liposomes in the atherosclerotic vessel wall. In: Bioconjugate Chemistry. 2019.
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title = "Multimodal positron emission tomography imaging to quantify uptake of 89Zr-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.",
author = "Lobatto, {Mark E.} and Tina Binderup and Robson, {Philip M.} and Giesen, {Luuk F.P.} and Claudia Calcagno and Julia Witjes and Francois Fay and Samantha Baxter and Wessel, {Chang Ho} and Mootaz Eldib and Jason Bini and Carlin, {Sean D.} and Stroes, {Erik S.G.} and Gert Storm and Andreas Kjaer and Lewis, {Jason S.} and Thomas Reiner and Fayad, {Zahi A.} and Mulder, {Willem J.M.} and Carlos P{\'e}rez-Medina",
year = "2019",
month = "5",
day = "16",
doi = "10.1021/acs.bioconjchem.9b00256",
language = "English",
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Lobatto, ME, Binderup, T, Robson, PM, Giesen, LFP, Calcagno, C, Witjes, J, Fay, F, Baxter, S, Wessel, CH, Eldib, M, Bini, J, Carlin, SD, Stroes, ESG, Storm, G, Kjaer, A, Lewis, JS, Reiner, T, Fayad, ZA, Mulder, WJM & Pérez-Medina, C 2019, 'Multimodal positron emission tomography imaging to quantify uptake of 89Zr-labeled liposomes in the atherosclerotic vessel wall', Bioconjugate Chemistry. https://doi.org/10.1021/acs.bioconjchem.9b00256

Multimodal positron emission tomography imaging to quantify uptake of 89Zr-labeled liposomes in the atherosclerotic vessel wall. / Lobatto, Mark E.; Binderup, Tina; Robson, Philip M.; Giesen, Luuk F.P.; Calcagno, Claudia; Witjes, Julia; Fay, Francois; Baxter, Samantha; Wessel, Chang Ho; Eldib, Mootaz; Bini, Jason; Carlin, Sean D.; Stroes, Erik S.G.; Storm, Gert; Kjaer, Andreas; Lewis, Jason S.; Reiner, Thomas; Fayad, Zahi A.; Mulder, Willem J.M. (Corresponding author); Pérez-Medina, Carlos (Corresponding author).

In: Bioconjugate Chemistry, 16.05.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Multimodal positron emission tomography imaging to quantify uptake of 89Zr-labeled liposomes in the atherosclerotic vessel wall

AU - Lobatto, Mark E.

AU - Binderup, Tina

AU - Robson, Philip M.

AU - Giesen, Luuk F.P.

AU - Calcagno, Claudia

AU - Witjes, Julia

AU - Fay, Francois

AU - Baxter, Samantha

AU - Wessel, Chang Ho

AU - Eldib, Mootaz

AU - Bini, Jason

AU - Carlin, Sean D.

AU - Stroes, Erik S.G.

AU - Storm, Gert

AU - Kjaer, Andreas

AU - Lewis, Jason S.

AU - Reiner, Thomas

AU - Fayad, Zahi A.

AU - Mulder, Willem J.M.

AU - Pérez-Medina, Carlos

PY - 2019/5/16

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N2 - 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.

AB - 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.

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