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

David Vancraeynest (1, 2, 3) , Véronique Roelants (1, 4) , Caroline Bouzin (1) , François-Xavier Hanin (1, 4) , Stephan Walrand (1, 4) , Vanesa Bol (1, 4) , Anne Bol (1, 4) , Anne-Catherine Pouleur (2, 1, 3) , Agnès Pasquet (5, 2, 1) , Bernhard Gerber (2, 1, 5) , Philippe Lesnik (5) , Thierry Huby (5) , François Jamar (1, 4) , Jean-Louis Vanoverschelde (4, 2, 1, 3)

1 IREC - Institut de Recherche Expérimentale et Clinique
2 CARD - Pôle de Recherche Cardiovasculaire
3 Division of Cardiology
4 MIRO - Pôle d’Imagerie Médicale, Radiothérapie et Oncologie
5 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases

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.

Mots clés: αVβ3 integrin; Maraciclatide; Vulnerable atherosclerotic plaque; SPECT imaging

Domaines: Médecine humaine et pathologie

David Vancraeynest, Véronique Roelants, Caroline Bouzin, François-Xavier Hanin, Stephan Walrand, et al.. αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice. EJNMMI Research, 2016, 6, pp.29. ⟨10.1186/s13550-016-0184-9⟩. ⟨hal-01298089⟩