CXCR4-targeted sensitive magnetic particle imaging for abdominal aortic aneurysm early detection and prognosis evaluation by recognizing total inflammatory cells

Abstract

Background The maximum aortic diameter remains the diagnostic criteria and the indicator for prognosis prediction of abdominal aortic aneurysms (AAA). An additional imaging modality is currently needed to help evaluate the prognosis of AAA as well as early detection of AAA formation. This study evaluated the most effective inflammatory markers for AAA using single-cell sequencing and, from these, developed probes to facilitate in vivo multimodal imaging of AAA inflammation. Methods and Results Single-cell RNA sequencing (scRNAseq) of the human aortic aneurysms, GSE155468 and GSE166676 datasets, identified CXCR4 as the most representative marker. Anti-CXCR4-PE antibody was conjugated to superparamagnetic iron oxide nanoparticles to synthesise Fe3O4-anti-CXCR4-PE probes. The biocompatibility and specificity of the probes were validated in vivo and in vitro. Magnetic particle imaging (MPI) and fluorescence imaging (FLI) were performed to assess inflammation in early and advanced AAA mouse models. CXCR4-specific receptor inhibitor, AMD3100, was used for confirming CXCR4 as an excellent target for AAA imaging and therapy. scRNAseq indicated that chemokine-related pathways were upregulated in aortic aneurysms, and CXCR4 was the chemokine receptor that markers all AAA-related immune cells and inflammatory vascular cells. Fe3O4-anti-CXCR4-PE effectively recognised immune cells and inflammatory vascular cells, as strong MPI and FLI signals corresponded to increased CXCR4, CD45, and CD68 levels which represented AAA severity and rupture risk. Importantly, Fe3O4-anti-CXCR4-PE can help identify early AAA formation when ultrasound is undiagnosable. Finally, AMD3100 treatment in AAA mouse model inhibited AAA expansion and rupture and reduced aortic wall inflammation by inhibiting accumulation of immune cells and hematopoietic stem cells. Conclusion CXCR4 markers immune cells and inflammatory vascular cells in AAA and is associated with AAA prognosis in a mouse model of AAA. CXCR4-targeting multimodal MPI/FLI provides a novel approach for AAA prognosis prediction and early detection.