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αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.

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Vancraeynest, David [UCL] Roelants, Véronique [UCL] Bouzin, Caroline [UCL] Hanin, François-Xavier [UCL] Walrand, Stéphan [UCL] Bol, Vanesa [UCL] Bol, Anne [UCL] Pouleur, Anne-Catherine [UCL] Pasquet, Agnes [UCL] Gerber, Bernhard [UCL] Jamar, François [UCL] Vanoverschelde, Jean-Louis [UCL]

(eng) Background: αVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated 99mTc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice. Methods: Apolipoprotein E-negative (ApoE−/−) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with 99mTc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE−/− mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology. Results: Tracer uptake was significantly higher in ApoE−/− mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 99mTc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73). Conclusions: 99mTc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for identifying high-risk plaques in patients.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2016
Language Anglais
Journal information "E J N M M I Research" - Vol. 6, no. 1, p. 29 [1-9] (2016)
Peer reviewed yes
Publisher SpringerOpen ((Germany) Heidelberg)
e-issn 2191-219X
Publication status Publié
Affiliations UCL - SSS/IREC/CARD-Pôle de recherche cardiovasculaire
UCL - (SLuc) Service de cardiologie
UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - (SLuc) Service de médecine nucléaire
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Bibliographic reference Vancraeynest, David ; Roelants, Véronique ; Bouzin, Caroline ; Hanin, François-Xavier ; Walrand, Stéphan ; et. al. αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.. In: E J N M M I Research, Vol. 6, no. 1, p. 29 [1-9] (2016)
Permanent URL http://hdl.handle.net/2078.1/182099