18F-choline images murine atherosclerotic plaques ex vivo.
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.


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.
Matter
Christian M
CM
Cardiovascular Research, Institute of Physiology, University of Zurich, Cardiovascular Center, Switzerland. cmatter@physiol.unizh.ch
Wyss
Matthias T
MT
Meier
Patricia
P
Späth
Nicolas
N
von Lukowicz
Tobias
T
Lohmann
Christine
C
Weber
Bruno
B
Ramirez de Molina
Ana
A
Lacal
Juan Carlos
JC
Ametamey
Simon M
SM
von Schulthess
Gustav K
GK
Lüscher
Thomas F
TF
Kaufmann
Philipp A
PA
Buck
Alfred
A
D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000201:enzymology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000276:immunology; D001345:Autoradiography; D002794:Choline / Q000493:pharmacokinetics; D002797:Choline Kinase / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity
D001057:Apolipoproteins E; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002797:Choline Kinase; D002794:Choline