Published Online
on May 13, 2009

A more recent version of this article appeared on July 1, 2009

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Original Article

Evaluation of vβ3 Integrin -targeted PET Tracer ¹⁸F–Galacto–RGD for Imaging of Vascular Inflammation in Atherosclerotic Mice

Iina Laitinen^1,5; Antti Saraste²; Eliane Weidl²; Thorsten Poethko²; Axel W. Weber²; Stephan G. Nekolla²; Pia Leppänen³; Seppo Ylä–Herttuala³; Gabriele Hölzlwimmer⁴; Axel Walch⁴; Irene Esposito⁴; Hans–Jürgen Wester²; Juhani Knuuti¹ and Markus Schwaiger²

¹ University of Turku, Turku, Finland;
² Technische Universität München, München, Germany;
³ University of Kuopio, Kuopio, Finland;
⁴ Helmholtz Zentrum München, München/Neuherberg, Germany

⁵ E-mail: iina.laitinen{at}tyks.fi

Background—¹⁸F–Galacto–RGD is a positron emission tomography (PET) tracer binding to vβ3 integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated ¹⁸F–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 western diet and normally fed adult C57BL/6 control mice were injected with ¹⁸F–galacto–RGD and ³H–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 ¹⁸F–galacto–RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal ¹⁸F–galacto–RGD uptake in the atherosclerotic plaques when compared to the adjacent, normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. While angiogenesis was not detected, ¹⁸F–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 18F-galacto-RGD uptake co-localizing with calcified lesions of the aortic arch as seen in CT angiography.

Conclusions—¹⁸F–Galacto–RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. ¹⁸F–Galacto–RGD is a potential tracer for non-invasive imaging of inflammation in atherosclerotic lesions.

Key Words: atherosclerosis • imaging • inflammation • plaque • radioisotopes