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*, Carlos Pérez-Medina*

*Corresponding author for this work

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
Pages (from-to)360-368
Number of pages9
JournalBioconjugate chemistry
Volume31
Issue number2
Early online date16 May 2019
DOIs
Publication statusPublished - 19 Feb 2020

    Fingerprint

Keywords

  • UT-Hybrid-D

Cite this

Lobatto, M. E., Binderup, T., Robson, P. M., Giesen, L. F. P., Calcagno, C., Witjes, J., ... Pérez-Medina, C. (2020). Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall. Bioconjugate chemistry, 31(2), 360-368. https://doi.org/10.1021/acs.bioconjchem.9b00256