Monitoring of macrophage accumulation in statin-treated atherosclerotic mouse model using sodium iodide symporter imaging system.

INTRODUCTION:Macrophages play a key role in atherosclerotic plaque formation in atherosclerosis, but its detailed understanding has poorly investigated until now. Thus, we sought to demonstrate a noninvasive technique for macrophage tracking to atherosclerotic lesions in apolipoprotein E-/-(ApoE-/-) mice with an imaging system based on sodium iodide symporter (NIS) gene coupled with 99mTc-single-photon emission computed tomography (SPECT). METHODS AND RESULTS:Macrophage cells (RAW264.7) were stably transduced with retrovirus expressing NIS gene (RAW-NIS). In RAW-NIS cells, uptake of 125I was higher than the parental cells. [18F]FDG signals in the aorta at 30weeks on an ApoE-/- mice with high cholesterol diet were higher (1.7±0.12% injected dose (ID)) than those in control group (0.84±0.06% ID). Through 99mTc-SPECT/computed tomography (CT), in the RAW-NIS cell injected group, the 99mTc-pertechnetate uptake in aorta was higher than control groups. However, according to atorvastatin treatment, RAW-NIS cell recruitment reduced to the aorta. Area of 99mTc-pertechnetate uptake was positively correlated with immunostaining results against macrophage antigen (CD68). Cholesterol and low-density lipoprotein levels of atorvastatin-treated group showed lower than those of atorvastatin-untreated group, but did not reach statistical difference. CONCLUSIONS:This novel approach to tracking macrophages to atherosclerotic plaques in vivo can be applied for studies of arterosclerotic vascular disease.