title: 99mTc-cAbVCAM1-5 imaging is a sensitive and reproducible tool for the detection of inflamed atherosclerotic lesions in mice.
abstract: (99m)Tc-cAbVCAM1-5, a single-domain antibody fragment directed against mouse or human vascular cell adhesion molecule 1 (VCAM-1), recently has been proposed as a new imaging agent for the detection of inflamed atherosclerotic lesions. Indeed, in a mouse model of atherosclerosis, (99m)Tc-cAbVCAM1-5 specifically bound to VCAM-1-positive lesions, thereby allowing their identification on SPECT images. The purpose of the present study was to investigate (99m)Tc-cAbVCAM1-5 imaging sensitivity using a reference statin therapy.
  
  
  METHODS
  Thirty apolipoprotein E-deficient mice were fed a western-type diet. First, the relationship between the level of VCAM-1 expression and (99m)Tc-cAbVCAM1-5 uptake was evaluated in 18 mice using immunohistochemistry and autoradiography. Second, longitudinal SPECT/CT imaging was performed on control (n = 9) or atorvastatin-treated mice (0.01% w/w, n = 9).
  
  
  RESULTS
  (99m)Tc-cAbVCAM1-5 uptake in atherosclerotic lesions correlated with the level of VCAM-1 expression (P < 0.05). Atorvastatin exerted significant antiatherogenic effects, and (99m)Tc-cAbVCAM1-5 lesion uptake was significantly reduced in 35-wk-old atorvastatin-treated mice, as indicated by ex vivo γ-well counting and autoradiography (P < 0.05). SPECT imaging quantification based on contrast-enhanced CT was reproducible (interexperimenter intraclass correlation coefficient, 0.97; intraexperimenter intraclass correlation coefficient, 0.90), and yielded results that were highly correlated with tracer biodistribution (r = 0.83; P < 0.0001). Therefore, reduced (99m)Tc-cAbVCAM1-5 uptake in atorvastatin-treated mice was successfully monitored noninvasively by SPECT/CT imaging (0.87 ± 0.06 vs. 1.11 ± 0.09 percentage injected dose per cubic centimeter in control group, P < 0.05).
  
  
  CONCLUSIONS
  (99m)Tc-cAbVCAM1-5 imaging allowed the specific, sensitive, and reproducible quantification of VCAM-1 expression in mouse atherosclerotic lesions. (99m)Tc-cAbVCAM1-5 therefore exhibits suitable characteristics for the evaluation of novel antiatherogenic agents.
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France alexis.broisat@inserm.fr.
authors.forename: Alexis
authors.initials: A
authors.lastname: Broisat
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Jakub
authors.initials: J
authors.lastname: Toczek
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Laurent S
authors.initials: LS
authors.lastname: Dumas
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Mitra
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bacot
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Perret
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Slimani
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France Cardiology Department, Grenoble University Hospital, Grenoble, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Barone-Rochette
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Soubies
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium; and.
authors.forename: Nick
authors.initials: N
authors.lastname: Devoogdt
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium; and Nuclear Medicine Department, UZ Brussel, Brussels, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fagret
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Laurent M
authors.initials: LM
authors.lastname: Riou
authors.affiliation: Unité 1039, INSERM, Grenoble, France Radiopharmaceutiques Biocliniques, Université Joseph Fourier Grenoble 1, Grenoble, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging*; D000069059:Atorvastatin; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D007128:Immunoglobulin Fragments; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods; D011758:Pyrroles / Q000494:pharmacology; D012016:Reference Values; D015203:Reproducibility of Results; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry*
chemical_list: D001057:Apolipoproteins E; D006538:Heptanoic Acids; D007128:Immunoglobulin Fragments; D011758:Pyrroles; D019010:Vascular Cell Adhesion Molecule-1; D013667:Technetium; D000069059:Atorvastatin
keywords: 99mTc-cAbVCAM1-5; VCAM-1; atherosclerosis; molecular imaging