title: Imaging VEGF receptor expression to identify accelerated atherosclerosis.
abstract: BACKGROUND
  The biology of the vulnerable plaque includes increased inflammation and rapid growth of vasa vasorum, processes that are associated with enhanced vascular endothelial growth factor (VEGF)/ imaging receptors for VEGF (VEGFR) signaling and are accelerated in diabetes. This study was designed to test the hypothesis that VEGFRs in atherosclerotic plaques with a SPECT tracer scVEGF-PEG-DOTA/(99m)Tc (scV/Tc) can identify accelerated atherosclerosis in diabetes.
  
  
  METHODS
  Male apolipoprotein E null (ApoE(-/-)) mice (6 weeks of age) were made diabetic (n = 10) or left as non-diabetic (n = 13). At 26 to 28 weeks of age, 5 non-diabetic mice were injected with functionally inactivated scV/Tc (in-scV/Tc) that does not bind to VEGF receptors, while 8 non-diabetic and 10 diabetic mice were injected with scV/Tc. After blood pool clearance, at 3 to 4 h post-injection, mice were injected with CT contrast agent and underwent SPECT/CT imaging. From the scans, regions of interest (ROI) were drawn on serial transverse sections comprising the proximal aorta and the percentage of injected dose (%ID) in ROIs was calculated. At the completion of imaging, mice were euthanized, proximal aorta explanted for gamma well counting to determine the percentage of injected dose per gram (%ID/g) uptake and immunohistochemical characterization.
  
  
  RESULTS
  The uptake of scV/Tc in the proximal aorta, calculated from SPECT/CT co-registered scans as %ID, was significantly higher in the diabetic mice (0.036 ± 0.017%ID) compared to non-diabetic mice (0.017 ± 0.005%ID; P < 0.01), as was uptake measured as %ID/g in harvested aorta, 1.81 ± 0.50%ID/g in the diabetic group vs. 0.98 ± 0.25%ID/g in the non-diabetic group (P < 0.01). The nonspecific uptake of in-scV/Tc in proximal aorta was significantly lower than the uptake of functionally active scV/Tc. Immunostaining of the atherosclerotic lesions showed higher expression of VEGFR-1 and VEGFR-2 in the diabetic mice.
  
  
  CONCLUSIONS
  These initial results suggest that imaging VEGFR with scV/Tc shows promise as a non-invasive approach to identify accelerated atherosclerosis.
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168th St, PH 10 center rm 203, New York, NY, 10032, USA, yt2166@cumc.columbia.edu.
authors.forename: Yared
authors.initials: Y
authors.lastname: Tekabe
authors.forename: Maria
authors.initials: M
authors.lastname: Kollaros
authors.forename: Adam
authors.initials: A
authors.lastname: Zerihoun
authors.forename: Geping
authors.initials: G
authors.lastname: Zhang
authors.forename: Marina V
authors.initials: MV
authors.lastname: Backer
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Backer
authors.forename: Lynne L
authors.initials: LL
authors.lastname: Johnson