Abstract 17541: Molecular Imaging of VEGF Receptors Predicts Vascular Remodeling in Transplant Vasculopathy
Introduction: Transplant vasculopathy (TV) is the major cause of late failure in solid organ transplantation. Vascular endothelial growth factor (VEGF) plays a causal role in many forms of vascular remodeling including TV. Little is known about VEGF receptors in TV. We used VEGF-based fluorescent tracer scVEGF/Cy (single-chain VEGF, site-specifically labeled with near-infrared fluorescent dye Cy5.5), to assess VEGF receptor (VEGFR) expression and functionality by molecular imaging in TV.
Methods and Results: Adjacent segments of human coronary arteries were transplanted into the abdominal aortas of severe combined immunodeficient (SCID) mice (n=27). Adoptive transfer of allogeneic human peripheral blood mononuclear cells (PBMCs) after transplantation led to significant neointima formation over a period of 4 weeks (0.67±0.16 vs 0.21±0.05 mm2 without PBMC transfer, n=5, p=0.004). VEGFR-1 but not VEGFR-2 mRNA expression was significantly increased in transplanted arteries following PBMC transfer (n= 6, p<0.05). scVEGF/Cy (10μg/mouse) was intravenously injected to transplant recipients 4 weeks after PBMC transfer. Near-infrared imaging at 24 hours demonstrated focal uptake of scVEGF/Cy in the transplanted coronary arteries (mean fluorescence intensity 192.92±70.32 in the PBMC group vs. 16.18±4.70 in the control, no PBMC group, n=7, p<0.0001). Uptake specificity was established using inactivated scVEGF/Cy in transplant recipients 4 weeks after PBMC transfer. scVEGF/Cy uptake in transplanted arteries correlated with intima (r=0.86, p<0.0001), lumen (r=−0.85, p<0.0001) and total vessel (r=0.75, p=0.002) areas, but not with the media (r=0.53, p>0.05) area. Flow cytometry demonstrated scVEGF binding and uptake by human endothelial cells and activated T cells in vitro.
Conclusions: Molecular imaging of VEGF receptors may serve as a diagnostic tool for detection of vascular remodeling in TV.
- © 2010 by American Heart Association, Inc.