In vitro uptake and metabolism of [14C]acetate in rabbit atherosclerotic arteries : biological basis for atherosclerosis imaging with [11C]acetate

Introduction: Detection of vulnerable plaques is critically important for the selection of appropriate treatment and/or the prevention of atherosclerosis and ensuing cardiovascular diseases. In order to clarify the utility of [11C]acetate for atherosclerosis imaging, we determined the uptake and metabolism of acetate by in vitro studies using rabbit atherosclerotic arteries and [14C]acetate. Methods: Rabbits were fed with a conventional (n = 5) or a 0.5% cholesterol diet (n = 6). One side of the iliac-femoral arteries was injured by a balloon catheter. Radioactivity levels in the iliac-femoral arteries were measured after incubation in DMEM containing [1-14C]acetate for 60 min (% dpm/mg tissue). Radioactive components in the homogenized arteries were partitioned into aqueous, organic, and residue fractions by the Folch method, and analyzed by thin-layer chromatography (TLC). Results: The radioactivity level in the injured arteries of rabbits fed with the 0.5% cholesterol diet (atherosclerotic arteries) was significantly higher than that in either the non-injured or injured arteries of rabbits fed with the conventional diet (p < 0.05) (% dpm/mg tissue: conventional diet groups; 0.022 ± 0.005 and 0.024 ± 0.007, cholesterol diet groups; 0.029 ± 0.007 and 0.034 ± 0.005 for non-injured and injured arteries). In metabolite analysis, most of the radioactivity was found in the aqueous fraction in each group (87.4-94.6% of total radioactivity in the arteries), and glutamate was a dominant component (67.4-69.7% of the aqueous fraction in the arteries). Conclusions: The level of [14C]acetate-derived radioactivity into the arteries was increased by balloon injury and the burden of a cholesterol diet. Water-soluble metabolites were the dominant components with radioactivity in the atherosclerotic lesions. These results provide a biological basis for imaging atherosclerotic lesions by PET using [11C]acetate.