title: PET molecular imaging of angiogenesis with a multiple tyrosine kinase receptor-targeted agent in a rat model of myocardial infarction.
abstract: OBJECTIVE
  Angiogenesis plays a major role in tissue remodeling and repair after myocardial infarction (MI), and imaging it could provide information on the healing process. During angiogenesis, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and Tie receptors are upregulated, and this study aimed to develop a C-11 positron emission tomography (PET) agent for imaging angiogenesis by targeting these receptors.
  
  
  METHODS
  A VEGFR-2/Tie-2/PDGFRα inhibitor (N-(6-{4-[3-(2-fluoro-5-trifluoromethyl-phenyl)-ureido]-phenoxy}-1H-benzoimidazol-2-yl)-2-(4-methyl-piperazin-1-yl)-acetamide (ATV-1)) was synthesized and labeled with C-11. MicroPET imaging of a rat MI model was compared to proteins expression by immunohistochemistry.
  
  
  RESULTS
  [(11)C]ATV-1 specifically accumulated in the infracted region of the left ventricular (LV) lateral wall more than in the interventricular septal wall, but not in sham-operated or healthy animals. Moreover, [(11)C]ATV-1 uptake in the LV significantly correlated with Tie-2, VEGFR-2, and PDGFRα expression.
  
  
  CONCLUSIONS
  Imaging angiogenesis in MI rats using [(11)C]ATV-1 and PET has been demonstrated. These results merit further research and development of more hydrophilic modified [(11)C]ATV-1 as a PET tracer.
authors.affiliation: Cyclotron-Radiochemistry-MicroPET Unit, Hadassah-Hebrew University Hospital, Jerusalem, 91120, Israel.
authors.forename: Samar
authors.initials: S
authors.lastname: Dissoki
authors.forename: Galith
authors.initials: G
authors.lastname: Abourbeh
authors.forename: Olga
authors.initials: O
authors.lastname: Salnikov
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging*; D018919:Neovascularization, Physiologic; D049268:Positron-Emission Tomography; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D000081:Acetamides; D020794:Receptor Protein-Tyrosine Kinases