αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.
(2016) E J N M M I Research — Vol. 6, n° 1, p. 29 [1-9] (2016)
Files
EJNMMIResearch2016629.pdf
Open Access - Adobe PDF
- 3.72 MB
Details
- Authors
- Abstract
- (en) 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.
- Affiliations
Citations
Vancraeynest, D., Roelants, V., Bouzin, C., Hanin, F.-X., Walrand, S., Bol, V., Bol, A., Pouleur, A.-C., Pasquet, A., Gerber, B., Lesnik, P., Huby, T., Jamar, F., & Vanoverschelde, J.-L. (2016). αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice. E J N M M I Research, 6(1), 29 [1-9]. https://doi.org/10.1186/s13550-016-0184-9 (Original work published 2016)