on December 15, 2005
Published online before print December 15, 2005, doi: 10.1161/01.ATV.0000200106.34016.18
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Submitted on July 5, 2005
Accepted on November 29, 2005
18F-Choline Images Murine Atherosclerotic Plaques Ex Vivo
Christian M. Matter *;
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.) 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, University Hospital Zurich, Switzerland.
* To whom correspondence should be addressed. 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.
Key words: atherosclerosis • macrophages • apolipoprotein E knockout mice • autoradiography • radionuclide
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