Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall.
Mark E LobattoTina BinderupPhilip M RobsonLuuk F P GiesenClaudia CalcagnoJulia WitjesFrancois FaySamantha BaxterChang Ho WesselMootaz EldibJason BiniSean D CarlinErik S G StroesGert StormAndreas KjaerJason S LewisThomas ReinerZahi A FayadWillem J M MulderCarlos Pérez-MedinaPublished in: Bioconjugate chemistry (2019)
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.
Keyphrases
- positron emission tomography
- computed tomography
- pet imaging
- contrast enhanced
- magnetic resonance imaging
- high resolution
- diffusion weighted imaging
- dual energy
- image quality
- pet ct
- drug delivery
- magnetic resonance
- high throughput
- minimally invasive
- low dose
- cancer therapy
- high dose
- endothelial cells
- pulmonary hypertension
- deep learning
- pulmonary arterial hypertension
- drug release
- coronary artery
- iron oxide
- ultrasound guided