Molecular imaging of vascular endothelial growth factor receptors in graft arteriosclerosis.
OBJECTIVE
Vascular endothelial growth factor (VEGF) signaling plays a key role in the pathogenesis of vascular remodeling, including graft arteriosclerosis. Graft arteriosclerosis is the major cause of late organ failure in cardiac transplantation. We used molecular near-infrared fluorescent imaging with an engineered Cy5.5-labeled single-chain VEGF tracer (scVEGF/Cy) to detect VEGF receptors and vascular remodeling in human coronary artery grafts by molecular imaging.


RESULTS
VEGF receptor specificity of probe uptake was shown by flow cytometry in endothelial cells. In severe combined immunodeficiency mice, transplantation of human coronary artery segments into the aorta followed by adoptive transfer of allogeneic human peripheral blood mononuclear cells led to significant neointima formation in the grafts over a period of 4 weeks. Near-infrared fluorescent imaging of transplant recipients at 4 weeks demonstrated focal uptake of scVEGF/Cy in remodeling artery grafts. Uptake specificity was demonstrated using an inactive homolog of scVEGF/Cy. scVEGF/Cy uptake predominantly localized in the neointima of remodeling coronary arteries and correlated with VEGF receptor-1 but not VEGF receptor-2 expression. There was a significant correlation between scVEGF/Cy uptake and transplanted artery neointima area.


CONCLUSIONS
Molecular imaging of VEGF receptors may provide a noninvasive tool for detection of graft arteriosclerosis in solid organ transplantation.
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Jiasheng
J
Zhang
Mahmoud
M
Razavian
Sina
S
Tavakoli
Lei
L
Nie
George
G
Tellides
Joseph M
JM
Backer
Marina V
MV
Backer
Jeffrey R
JR
Bender
Mehran M
MM
Sadeghi
D000818:Animals; D001161:Arteriosclerosis / Q000175:diagnosis*; D002232:Carbocyanines; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis*
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D040262:Receptors, Vascular Endothelial Growth Factor