Evaluation and comparison of [¹⁸F]FDG and [¹¹C]choline as atherosclerosis imaging agents

Objectives Macrophage infiltration is characteristics for atherosclerotic vulnerable plaques, and energy metabolism and cell proliferation are elevated in these macrophages. [¹⁸F]FDG is the most common tracer for vulnerable plaque imaging by PET, but blood sugar should affect the tracer accumulation. It is previously reported [¹¹C]choline can be applied for plaque detection for visualizing the synthesis of phospholipids. In this study, we compared [¹⁸F]FDG and [¹¹C]choline as atherosclerosis imaging agents. We also focused on macrophage polarization, since it is described that polarization of macrophage affects the development of atherosclerosis and plaque rapture.

Methods Macrophages were isolated from the mice peritoneum (M0), and polarized to M1 or M2 phenotype by LPS/IFNγ or IL-4/IL-13, respectively. Then, [¹⁸F]FDG (2hr) or [¹¹C]choline (0.5hr) uptake level was investigated in high glucose (4000 mg/L) or low glucose (1000 mg/L) condition. For in vivo studies, [¹⁸F]FDG or [¹¹C]choline was injected into apoE-/- mice, and the aortas were harvested for autoradiography.

Results [¹⁸F]FDG uptake to M0 macrophages was largely affected by glucose (low glucose: 37, high glucose: 3 %dose/mg protein). In contrast, the effect was small in [¹¹C]choline (low glucose: 10, high glucose: 8 %dose/mg protein). [¹⁸F]FDG uptake was higher in proatherogenic M1 than anti-inflammatory M2 macrophages, but polarization did not affect [¹¹C]choline uptake. Similar results were obtained in in vivo investigation ([¹⁸F]FDG; 2 and 0.6, [¹¹C]choline; 0.5 and 0.4 %dose/g for fasted and non-fasted, respectively). However, since the uptake of [¹⁸F]FDG to the non-atherosclerotic region was more largely decreased in non-fasted condition, target-to-non-target ratio (T/N) was lower in fasted condition (fasted: 4 , non-fasted: 14). T/N of [¹¹C]choline was 7 and 4 for fasted and non-fasted, respectively.

Conclusions [¹⁸F]FDG should be the preferable tracer in glucose level controllable patients, and [¹¹C]choline can be used as an alternative tracer in such as diabetes patients.