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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:584.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

¹⁸F-Choline Images Murine Atherosclerotic Plaques Ex Vivo

Christian M. Matter; Matthias T. Wyss; Patricia Meier; Nicolas Späth; Tobias von Lukowicz; Christine Lohmann; Bruno Weber; Ana Ramirez de Molina; Juan Carlos Lacal; Simon M. Ametamey; Gustav K. von Schulthess; Thomas F. Lüscher; Philipp A. Kaufmann; Alfred Buck

From Cardiovascular Research (C.M.M., P.M., T.v.L., C.L., T.F.L.), Institute of Physiology, University of Zurich, Cardiovascular Center, University Hospital Zurich and Center for Integrative Human Physiology (C.M.M., T.v.L., T.F.L., P.A.K.), University of Zurich, and Nuclear Medicine (M.T.W., N.S., B.W., G.K.v.S., A.B.), University Hospital Zurich, Switzerland; Instituto de Investigaciones Biomédicas (A.R.d.M., J.C.L.), CSIC, Madrid, Spain; Center for Radiopharmaceutical Science Paul Scherrer Institute (S.M.A., P.A.K.), Villigen, Switzerland; and Nuclear Cardiology (P.A.K.), University Hospital Zurich, Switzerland.

Correspondence to Christian M. Matter, MD, Cardiovascular Research, Institute of Physiology, Zurich University and CardioVascular Center, University Hospital Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. E-mail cmatter{at}physiol.unizh.ch

Objective— Current imaging modalities of atherosclerosis mainly visualize plaque morphology. Valuable insight into plaque biology was achieved by visualizing enhanced metabolism in plaque-derived macrophages using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Similarly, enhanced uptake of ¹⁸F-fluorocholine (¹⁸F-FCH) was associated with macrophages surrounding an abscess. As macrophages are important determinants of plaque vulnerability, we tested ¹⁸F-FCH for plaque imaging.

Methods and Results— We injected ¹⁸F-FCH (n=5) or ¹⁸F-FDG (n=5) intravenously into atherosclerotic apolipoprotein E-deficient mice. En face measurements of aortae isolated 20 minutes after ¹⁸F-FCH injections demonstrated an excellent correlation between fat stainings and autoradiographies (r=0.842, P<0.0001), achieving a sensitivity of 84% to detect plaques by ¹⁸F-FCH. In contrast, radiotracer uptake 20 minutes after ¹⁸F-FDG injections correlated less with en face fat stainings (r=0.261, P<0.05), reaching a sensitivity of 64%. Histological analyses of cross-sections 20 minutes after coinjections of ¹⁸F-FCH and ¹⁴C-FDG (n=3) showed that ¹⁸F-FCH uptake correlated better with fat staining (r=0.740, P<0.0001) and macrophage-positive areas (r=0.740, P<0.0001) than ¹⁴C-FDG (fat: r=0.236, P=0.29 and CD68 staining: r=0.352, P=0.11), respectively.

Conclusions— ¹⁸F-FCH identifies murine plaques better than ¹⁸F-FDG using ex vivo imaging. Enhanced ¹⁸F-FCH uptake into macrophages may render this tracer a promising candidate for imaging plaques in patients.

For imaging plaque biology, we compared ex vivo autoradiographies and fat stainings of murine atherosclerotic aortae after injections of ¹⁸F-fluorocholine (¹⁸F-FCH) or ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). En face macroscopical and histological correlations were better for ¹⁸F-FCH as compared with ¹⁸F-FDG. Thus, ¹⁸F-FCH may be a promising compound for imaging plaques in patients.

Key Words: atherosclerosis • macrophages • apolipoprotein E knockout mice • autoradiography • radionuclide

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