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Original Articles

Evaluation of _vβ₃ Integrin-Targeted Positron Emission Tomography Tracer ¹⁸F-Galacto-RGD for Imaging of Vascular Inflammation in Atherosclerotic Mice

Iina Laitinen, MSc^*; Antti Saraste, MD, PhD^*; Eliane Weidl, PhD; Thorsten Poethko, PhD; Axel W. Weber, MSc; Stephan G. Nekolla, PhD; Pia Leppänen, PhD; Seppo Ylä-Herttuala, MD, PhD; Gabriele Hölzlwimmer, DVM; Axel Walch, MD; Irene Esposito, MD; Hans-Jürgen Wester, PhD; Juhani Knuuti, MD, PhD and Markus Schwaiger, MD

From the Nuklearmedizinische Klinik der TU Muenchen, Technische Universitaet Muenchen, Munich, Germany (A.S., E.W., T.P., A.W.W., S.G.N., H.-J.W., M.S.); Turku PET Centre, University of Turku, Turku, Finland (I.L., A.S., J.K.); Institute of Pathology, Helmholtz Zentrum Muenchen, Munich, Germany (G.H., A.W., I.E.); Institute of Pathology, Technische Universitaet Muenchen, Munich, Germany (I.E.); and A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland (P.L., S.Y.-H.).

Correspondence to Markus Schwaiger, MD, Klinikum rechts der Isar, Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Ismaninger Str. 22, 81675 Muenchen, Germany. E-mail markus.schwaiger{at}tum.de

Received December 23, 2008; accepted May 11, 2009.

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 a 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 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, 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 colocalizing 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 noninvasive imaging of inflammation in atherosclerotic lesions.

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

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CLINICAL PERSPECTIVE

*Iina Laitinen and Dr Saraste contributed equally to this work.