Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis Journal Article


Authors: Senders, M. L.; Hernot, S.; Carlucci, G.; van de Voort, J. C.; Fay, F.; Calcagno, C.; Tang, J.; Alaarg, A.; Zhao, Y.; Ishino, S.; Palmisano, A.; Boeykens, G.; Meerwaldt, A. E.; Sanchez-Gaytan, B. L.; Baxter, S.; Zendman, L.; Lobatto, M. E.; Karakatsanis, N. A.; Robson, P. M.; Broisat, A.; Raes, G.; Lewis, J. S.; Tsimikas, S.; Reiner, T.; Fayad, Z. A.; Devoogdt, N.; Mulder, W. J. M.; Pérez-Medina, C.
Article Title: Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis
Abstract: Objectives: This study sought to develop an integrative positron emission tomography (PET) with magnetic resonance imaging (MRI) procedure for accurate atherosclerotic plaque phenotyping, facilitated by clinically approved and nanobody radiotracers. Background: Noninvasive characterization of atherosclerosis remains a challenge in clinical practice. The limitations of current diagnostic methods demonstrate that, in addition to atherosclerotic plaque morphology and composition, disease activity needs to be evaluated. Methods: We screened 3 nanobody radiotracers targeted to different biomarkers of atherosclerosis progression, namely vascular cell adhesion molecule (VCAM)-1, lectin-like oxidized low-density lipoprotein receptor (LOX)-1, and macrophage mannose receptor (MMR). The nanobodies, initially radiolabeled with copper-64 (64Cu), were extensively evaluated in Apoe–/– mice and atherosclerotic rabbits using a combination of in vivo PET/MRI readouts and ex vivo radioactivity counting, autoradiography, and histological analyses. Results: The 3 nanobody radiotracers accumulated in atherosclerotic plaques and displayed short circulation times due to fast renal clearance. The MMR nanobody was selected for labeling with gallium-68 (68Ga), a short-lived radioisotope with high clinical relevance, and used in an ensuing atherosclerosis progression PET/MRI study. Macrophage burden was longitudinally studied by 68Ga-MMR–PET, plaque burden by T2-weighted MRI, and neovascularization by dynamic contrast-enhanced (DCE) MRI. Additionally, inflammation and microcalcifications were evaluated by fluorine-18 (18F)-labeled fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) PET, respectively. We observed an increase in all the aforementioned measures as disease progressed, and the imaging signatures correlated with histopathological features. Conclusions: We have evaluated nanobody-based radiotracers in rabbits and developed an integrative PET/MRI protocol that allows noninvasive assessment of different processes relevant to atherosclerosis progression. This approach allows the multiparametric study of atherosclerosis and can aid in early stage anti-atherosclerosis drug trials. © 2019 The Authors
Keywords: molecular imaging; atherosclerosis; pet/mri; nanobody
Journal Title: JACC: Cardiovascular Imaging
Volume: 12
Issue: 10
ISSN: 1936-878X
Publisher: Elsevier Science, Inc.  
Date Published: 2019-01-01
Start Page: 2015
End Page: 2026
Language: English
DOI: 10.1016/j.jcmg.2018.07.027
PUBMED: 30343086
PROVIDER: scopus
PMCID: PMC6461528
DOI/URL:
Notes: Article -- Export Date: 1 October 2019 -- Source: Scopus
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