Comparison of ¹⁸F-fluoromethylcholine and ¹⁸F-fluorodeoxyglucose for the detection of inflamed atherosclerotic plaques in mice

Objectives Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) has been used for the detection of inflamed atherosclerotic plaques, but imaging of coronary arteries is limited by high physiological uptake in the myocardium. We compared ¹⁸F-fluoromethylcholine (¹⁸F-FMCH), a marker of phospholipid metabolism, and ¹⁸F-FDG for the detection of inflamed atherosclerotic plaques in mouse aorta.

Methods Hypercholesterolemic+diabetic IGF-II/LDLR^-/-ApoB^100/100 mice were injected with 10 MBq of ¹⁸F-FMCH (n=8, no fast) or ¹⁸F-FDG (n=8, 4-hour fast). Twenty or 90 minutes later, respectively, uptake of tracers was measured in the plaques and normal vessel wall by digital autoradiography of aortic sections. Radioactivity concentration was measured in the aorta, myocardium and blood by gamma counter. Plaque macrophages were detected by anti-Mac-3 immunohistochemical staining.

Results The aortas of all mice showed large, macrophage-rich plaques. Aortic autoradiography showed strong accumulation of both ¹⁸F-FMCH and ¹⁸F-FDG in the atherosclerotic plaques with comparable plaque-to-normal vessel wall ratios (2.7±0.3 vs. 2.4±0.4, p=0.06). The highest ¹⁸F-FMCH uptake, up to 4 times higher than in the normal vessel wall, was seen in the plaques with the highest macrophage density. Aorta-to-blood ratios of ¹⁸F-FMCH and ¹⁸F-FDG were similar (4.6±2.2 vs. 3.2±0.8, p=0.13), but uptake of ¹⁸F-FMCH in the myocardium was 88 % lower (% of injected activity /gram of tissue 8.2±3.1 vs. 68±28, p<0.001).

Conclusions PET tracer ¹⁸F-FMCH is taken up in inflamed atherosclerotic plaques in the mouse aorta. The uptake of ¹⁸F-FMCH in plaques is comparable with that of ¹⁸F-FDG, and its lower uptake in the myocardium could be beneficial for coronary artery imaging.