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Laitinen, I.* ; Saraste, A.* ; Weidl, E.* ; Poethko, T.* ; Weber, A.W.* ; Nekolla, S.G.* ; Leppänen, P.* ; Yla-Herttuala, S.* ; Hölzlwimmer, G. ; Walch, A.K. ; Esposito, I. ; Wester, H.J.* ; Knuuti, J.* ; Schwaiger, M.*

Evaluation of ανβ₃ integrin-targeted positron emission tomography tracer ¹⁸F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice.

Circ.-Cardiovasc. Imaging 2, 331-338 (2009)
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Background-F-18-Galacto-RGD is a positron emission tomography (PET) tracer binding to alpha(v)beta(3) integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated F-18-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose. Methods and results-Hypercholesterolemic LDLR(-/-)ApoB(100/100) mice on a Western diet and normally fed adult C57BL/6 control mice were injected with F-18-galacto-RGD and H-3-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of F-18-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal F-18-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, F-18-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized F-18-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. Conclusions- F-18-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. F-18-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter atherosclerosis; imaging; inflammation; plaque; radioisotopes; acute myocardial-infarction; plaque inflammation; mouse model; angiogenesis; expression; disease; pet; hypercholesterolemia; neovascularization; nanoparticles
ISSN (print) / ISBN 1941-9651
e-ISSN 1942-0080
Zeitschrift Circulation: Cardiovascular Imaging
Quellenangaben Band: 2, Heft: 4, Seiten: 331-338 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus