title: Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs.
abstract: BACKGROUND
  Receptor for advanced glycated end product (RAGE) expression is a prominent feature of atherosclerosis. We have previously shown in apoE null mice uptake of a radiolabeled anti-RAGE antibody in atherosclerotic plaque and now evaluate RAGE-directed imaging to identify advanced plaques in a large animal model.
  
  
  METHODS
  Nine hyperlipidemic (HL) pigs were injected with 603.1 ± 129.5 MBq of (99m)Tc-anti-RAGE F(ab')2, and after 6 h (blood pool clearance), they underwent single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of the neck, thorax, and hind limbs. Two HL pigs received (99m)Tc non-immune IgG F(ab')2, and three farm pigs were injected with (99m)Tc-anti-RAGE F(ab')2. After imaging, the pigs were euthanized. The aorta from the root to bifurcation was dissected, and the innominates, proximal carotids, and coronaries were dissected and counted, stained for H&E and RAGE, and AHA-classified.
  
  
  RESULTS
  On pathology, 24% of the arterial segments showed AHA class III or IV lesions, and these lesions were confined almost exclusively to coronaries and carotids with % stenosis from 15% to 65%. Scatter plots of %ID/g for class III/IV vs. I/II lesions showed almost complete separation. Focal vascular uptake of tracer visualized on SPECT scans corresponded to class III/IV lesions in the coronary and carotid vessels. In addition, uptake in the hind limbs was noted in the HL pigs and corresponded to RAGE staining of small arteries in the muscle sections. Correlations for the vascular lesions were r = 0.747, P = 0.001 for %ID vs. %ID/g and r = 0.83, P = 0.002 for %ID/g vs. % RAGE staining.
  
  
  CONCLUSIONS
  Uptake of radiolabeled anti-RAGE antibody in coronary and carotid fibroatheroma and in the small arteries of the hind limbs in a relevant large animal model of atherosclerosis supports the important role of RAGE in atherosclerosis and peripheral artery disease as a target for imaging and treatment.
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: Lynne L
authors.initials: LL
authors.lastname: Johnson
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: Yared
authors.initials: Y
authors.lastname: Tekabe
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kollaros
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Eng
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: Ketan
authors.initials: K
authors.lastname: Bhatia
authors.affiliation: Department of Medicine, Columbia University Medical Center, 622 West 168 St, New York 10032, NY, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Veterinary Medicine, University of Wisconsin, Madison 53706, WI, USA.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Krueger
authors.affiliation: Department of Veterinary Medicine, University of Wisconsin, Madison 53706, WI, USA.
authors.forename: Dhanansayan
authors.initials: D
authors.lastname: Shanmuganayagam
authors.affiliation: Department of Medicine, NYU Medical Center, New York 10016, NY, USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
keywords: Atherosclerosis; Hyperlipidemic pigs; Imaging; RAGE