Gezim Bala1, Anneleen Blykers2, Catarina Xavier2, Benedicte Descamps3, Alexis Broisat4, Catherine Ghezzi4, Daniel Fagret4, Guy Van Camp2, Vicky Caveliers5, Christian Vanhove3, Tony Lahoutte5, Steven Droogmans6, Bernard Cosyns6, Nick Devoogdt2, Sophie Hernot2. 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. Published on behalf of the European Society of Cardiology. All rights reserved.
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 murineatherosclerotic 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 humanVCAM-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. Published on behalf of the European Society of Cardiology. All rights reserved.
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