CD93 in macrophages: A novel target for atherosclerotic plaque imaging?

Noninvasive imaging atherosclerotic (AS) plaque is of great importance for early diagnosis. Recently, CD93 in M phi was linked to atherosclerosis development. Herein, we have investigated whether CD93 in M phi is a potential novel target for atherosclerotic plaque imaging. CD93(hi) and CD93(lo) M phi were prepared with or without LPS stimulation, before biological activity was evaluated. A rat AS model was produced with left carotid artery clamped. Whole-body/ex vivo phosphor autoradiography of the artery and biodistribution were investigated after incorporation of H-3-2-DG into CD93(hi) and CD93(lo) M phi or after I-125-alpha-CD93 (I-125-anti-CD93mAb) injection. The plaque tissue was subjected to CD93/CD68 immunofluorescence/immunohistochemistry staining. CD93(hi) and CD93(lo) M phi cells were successfully prepared without significant effect on bioactivity after incorporative labelled with H-3-2-DG. The AS model was successfully established. Biodistribution studies showed that adoptive transfer of H-3-2-DG-CD93(hi) M phi or I-125- alpha-CD93 injection resulted in accumulation of radioactivity within the atherosclerotic plaque in the clamped left carotid artery. T/NT (target/non-target, left/right carotid artery) ratio was higher in the H-3-2-DG-CD93(hi) M phi adoptive transfer group than in the H-3-2-DG-CD93(lo) M phi group (p < .05). Plaque radioactivity in the I-125-alpha-CD93 injection group was significantly higher than in the I-125-IgG control group (p < .01). The higher radioactivity accumulated in the clamped left carotid artery was confirmed by phosphor autoradiography. More importantly, CD93/CD68 double-positive M phi accumulated at the atherosclerotic plaque in H-3-2-DG-CD93(hi) M phi adoptive transfer group, which correlated with plaque radioactivity (r = .99, p < .01). In summary, both adoptive-transferred H-3-2-DG-labelled CD93(hi) M phi and I-125-alpha-CD93 injection specifically targeted CD93 in atherosclerotic plaque. CD93 is a potential target in atherosclerotic plaque imaging.