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Eur Heart J Cardiovasc Imaging. 2016 Sep;17(9):1001-8. doi: 10.1093/ehjci/jev346. Epub 2016 Jan 22.

Targeting of vascular cell adhesion molecule-1 by 18F-labelled nanobodies for PET/CT imaging of inflamed atherosclerotic plaques.

Author information

1
Centrum voor Hart-en Vaatziekten (CHVZ), UZ Brussel, Brussels, Belgium In Vivo Cellular and Molecular Imaging (ICMI), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels B-1090, Belgium gezim.bala@vub.ac.be.
2
In Vivo Cellular and Molecular Imaging (ICMI), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels B-1090, Belgium.
3
iMinds-IBiTech-MEDISIP, Department of Electronics and Information Systems, Universiteit Gent, Ghent, Belgium.
4
Radiopharmaceutiques Biocliniques, INSERM, 1039-Université de Grenoble, La Tronche, France.
5
In Vivo Cellular and Molecular Imaging (ICMI), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels B-1090, Belgium Nuclear Medicine Department, UZ Brussel, Brussels, Belgium.
6
Centrum voor Hart-en Vaatziekten (CHVZ), UZ Brussel, Brussels, Belgium In Vivo Cellular and Molecular Imaging (ICMI), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels B-1090, Belgium.

Abstract

AIMS:

Positron emission tomography-computed tomography (PET-CT) is a highly sensitive clinical molecular imaging modality to study atherosclerotic plaque biology. Therefore, we sought to develop a new PET tracer, targeting vascular cell adhesion molecule (VCAM)-1 and validate it in a murine atherosclerotic model as a potential agent to detect atherosclerotic plaque inflammation.

METHODS AND RESULTS:

The anti-VCAM-1 nanobody (Nb) (cAbVCAM-1-5) was radiolabelled with Fluorine-18 ((18)F), with a radiochemical purity of >98%. In vitro cell-binding studies showed specific binding of the tracer to VCAM-1 expressing cells. In vivo PET/CT imaging of ApoE(-/-) mice fed a Western diet or control mice was performed at 2h30 post-injection of [(18)F]-FB-cAbVCAM-1-5 or (18)F-control Nb. Additionally, plaque uptake in different aorta segments was evaluated ex vivo based on extent of atherosclerosis. Atherosclerotic lesions in the aortic arch of ApoE(-/-) mice, injected with [(18)F]-FB-anti-VCAM-1 Nb, were successfully identified using PET/CT imaging, while background signal was observed in the control groups. These results were confirmed by ex vivo analyses where uptake of [(18)F]-FB-cAbVCAM-1-5 in atherosclerotic lesions was significantly higher compared with control groups. Moreover, uptake increased with the increasing extent of atherosclerosis (Score 0: 0.68 ± 0.10, Score 1: 1.18 ± 0.36, Score 2: 1.49 ± 0.37, Score 3: 1.48 ± 0.38%ID/g, Spearman's r(2) = 0.675, P < 0.0001). High lesion-to-heart, lesion-to-blood, and lesion-to-control vessel ratios were obtained (12.4 ± 0.4, 3.3 ± 0.4, and 3.1 ± 0.6, respectively).

CONCLUSION:

The [(18)F]-FB-anti-VCAM-1 Nb, cross-reactive for both mouse and human VCAM-1, allows non-invasive PET/CT imaging of VCAM-1 expression in atherosclerotic plaques in a murine model and may represent an attractive tool for imaging vulnerable atherosclerotic plaques in patients.

KEYWORDS:

PET/CT; VCAM-1; atherosclerosis; molecular imaging; nanobody

PMID:
26800768
DOI:
10.1093/ehjci/jev346
[Indexed for MEDLINE]

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