Journal
BIOCONJUGATE CHEMISTRY
Volume 31, Issue 2, Pages 360-368Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.9b00256
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Funding
- National Heart, Lung, and Blood Institute, National Institutes of Health, as a Program of Excellence in Nanotechnology (PEN) Award [HHSN268201000045C]
- NIH/NHLBI [R01 HL071021, R01 HL118440, R01 HL125703]
- NIH/NLBIB [R01 EB009638]
- NWO Vidi [91713324]
- FP7 NANOATHERO
- Dutch network for Nanotechnology NanoNextNL in the subprogram Drug Delivery
- International Atherosclerosis Society
- foundation De Drie Lichten in The Netherlands
- Danish Council for Independent Research (DFF) [1333-00235A]
- Danish Cancer Society [R71-A4285]
- Rigshospitalets Research Foundation
- NIH MSKCC Center [P30-CA08748]
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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 (Zr-89). 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-MR and ex vivo using near-infrared fluorescence (NIRF) imaging. The Zr-89-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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