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

Abstract

Noninvasive imaging atherosclerotic (AS) plaque is of great importance for early diagnosis. Recently, CD93 in MΦ was linked to atherosclerosis development. Herein, we have investigated whether CD93 in MΦ is a potential novel target for atherosclerotic plaque imaging. CD93^hi and CD93^lo MΦ 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 ³ H-2-DG into CD93^hi and CD93^lo MΦ or after ¹²⁵ I-α-CD93 (¹²⁵ I-anti-CD93mAb) injection. The plaque tissue was subjected to CD93/CD68 immunofluorescence/immunohistochemistry staining. CD93^hi and CD93^lo MΦ cells were successfully prepared without significant effect on bioactivity after incorporative labelled with ³ H-2-DG. The AS model was successfully established. Biodistribution studies showed that adoptive transfer of ³ H-2-DG-CD93^hi MΦ or ¹²⁵ I- α-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 ³ H-2-DG-CD93^hi MΦ adoptive transfer group than in the ³ H-2-DG-CD93^lo MΦ group (p < .05). Plaque radioactivity in the ¹²⁵ I-α-CD93 injection group was significantly higher than in the ¹²⁵ I-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 MΦ accumulated at the atherosclerotic plaque in ³ H-2-DG-CD93^hi MΦ adoptive transfer group, which correlated with plaque radioactivity (r = .99, p < .01). In summary, both adoptive-transferred ³ H-2-DG-labelled CD93^hi MΦ and ¹²⁵ I-α-CD93 injection specifically targeted CD93 in atherosclerotic plaque. CD93 is a potential target in atherosclerotic plaque imaging.

Keywords: CD93; atherosclerosis; macrophage; molecular imaging; radionuclide.