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.