title: Targeted ED-B fibronectin SPECT in vivo imaging in experimental atherosclerosis.
abstract: OBJECTIVE
  The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [(99m)Tc]-conjugated AP39 ([(99m)Tc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice.
  
  
  METHODS
  Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [(99m)Tc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry.
  
  
  RESULTS
  In vivo [(99m)Tc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236 ± 40.646 cpm/cm³) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468 ± 4.976 cpm/cm³) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P<0.01).
  
  
  CONCLUSIONS
  [(99m)Tc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.
authors: Department of Medicine - thore@dhzb.de.
authors: T
authors: T
authors: Dietrich
authors: D
authors: D
authors: Berndorff
authors: T
authors: T
authors: Heinrich
authors: T
authors: T
authors: Hucko
authors: E
authors: E
authors: Stepina
authors: P
authors: P
authors: Hauff
authors: L M
authors: LM
authors: Dinkelborg
authors: K
authors: K
authors: Atrott
authors: L
authors: L
authors: Giovannoni
authors: D
authors: D
authors: Neri
authors: E
authors: E
authors: Fleck
authors: K
authors: K
authors: Graf
authors: H D
authors: HD
authors: Menssen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005353:Fibronectins / Q000378:metabolism*; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013667:Technetium / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D015415:Biomarkers; C067625:FN1 protein, human; D005353:Fibronectins; D013667:Technetium