Abstract 11274: Non-Invasive in vivo Imaging of Peripheral Mononuclear Cell Migration to Atherosclerosis in Humans
Introduction: Based on the close correlation between plaque monocyte-derived macrophage content and plaque vulnerability, decreasing monocyte influx into the plaque is considered a promising target. Here, we demonstrate PBMC trafficking to advanced atherosclerotic plaques in humans.
Methods: To exclude activation of PBMCs after isolation, we performed flow cytometry on CD62 ligand (CD62L) expression in unmanipulated blood and after PBMC isolation. Patients (n=10) with metabolically active atherosclerotic plaques (defined as target-to-background ratio (TBR) ≥1.8 on positron emission tomography (PET)) and age-matched healthy controls (n=4) were included. Autologous PBMCs (20x106) were isolated using ficoll, labelled with Technetium-99 (99mTc; 200 MBq) and re-injected intravenously. Single Photon Emission Computed Tomography (SPECT/CT) was performed at 3, 4.5 and 6 hours post re-infusion (p.i.). Arterial wall PBMC influx was assessed via TBR by dividing uptake of arterial wall by venous blood pool.
Results: After 99mTc-labelling procedure, no activation of PBMCs was observed (MFI of CD62L at baseline 61.95% vs. after labelling 60.90%, p = ns). Following re-infusion of 99mTc-PBMCs, a time-dependent increase PBMC accumulation was observed in the atherosclerotic lesions (maximum TBR on SPECT/CT 3.23±0.85 at 3hr; 5.48±0.20 at 4.5hr; 7.30±1.33; all p<0.01 vs 3hr p.i.), accomponied by a significant correlation between areas with increased PBMC accumulation and metabolically active plaques on PET/CT (r=0.62; p<0.05). In contrast, no PBMC influx on SPECT/CT was observed in healthy controls.
Conclusion: We show a preferential increase in trafficking of PBMCs to metabolically active atherosclerotic lesions in patients. In contrast, trafficking to the arterial wall in controls as well as to non-atherogenic areas in patients is minimal. This non-invasive strategy enables us to evaluate novel compounds aimed at reducing the influx of PBMCs into the plaque.
- © 2013 by American Heart Association, Inc.