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

Gezim Bala, Anneleen Blykers, Catarina Xavier, Benedicte Descamps, Alexis Broisat, Catherine Ghezzi, Daniel Fagret, Guy Van Camp, Vicky Caveliers, Christian Vanhove, Tony Lahoutte, Steven Droogmans, Bernard Cosyns, Nick Devoogdt, Sophie Hernot

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1001-1008
JournalEuropean Heart Journal - Cardiovascular Imaging
Volume17
Issue number9
Early online date22 Jan 2016
DOIs
Publication statusPublished - Sep 2016

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