title: Imaging of VEGF receptor in a rat myocardial infarction model using PET.
abstract: Myocardial infarction (MI) leads to left ventricular (LV) remodeling, which leads to the activation of growth factors such as vascular endothelial growth factor (VEGF). However, the kinetics of a growth factor's receptor expression, such as VEGF, in the living subject has not yet been described. We have developed a PET tracer (64Cu-DOTA-VEGF121 [DOTA is 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid]) to image VEGF receptor (VEGFR) expression after MI in the living subject.
  
  
  METHODS
  In Sprague-Dawley rats, MI was induced by ligation of the left coronary artery and confirmed by ultrasound (n = 8). To image and study the kinetics of VEGFRs, 64Cu-DOTA-VEGF121 PET scans were performed before MI induction (baseline) and on days 3, 10, 17, and 24 after MI. Sham-operated animals served as controls (n = 3).
  
  
  RESULTS
  Myocardial origin of the 64Cu-DOTA-VEGF121 signal was confirmed by CT coregistration and autoradiography. VEGFR specificity of the 64Cu-DOTA-VEGF121 probe was confirmed by in vivo use of a 64Cu-DOTA-VEGFmutant. Baseline myocardial uptake of 64Cu-DOTA-VEGF121 was minimal (0.30 +/- 0.07 %ID/g [percentage injected dose per gram of tissue]); it increased significantly after MI (day 3, 0.97 +/- 0.05 %ID/g; P < 0.05 vs. baseline) and remained elevated for 2 wk (up to day 17 after MI), after which time it returned to baseline levels.
  
  
  CONCLUSIONS
  We demonstrate the feasibility of imaging VEGFRs in the myocardium. In summary, we imaged and described the kinetics of 64Cu-DOTA-VEGF121 uptake in a rat model of MI. Studies such as the one presented here will likely play a major role when studying pathophysiology and assessing therapies in different animal models of disease and, potentially, in patients.
authors: Molecular Imaging Program at Stanford, Department of Radiology, Division of Nuclear Medicine, Stanford University, Stanford, CA 94305-5427, USA.
authors: Martin
authors: M
authors: Rodriguez-Porcel
authors: Weibo
authors: W
authors: Cai
authors: Olivier
authors: O
authors: Gheysens
authors: Jürgen K
authors: JK
authors: Willmann
authors: Kai
authors: K
authors: Chen
authors: Hui
authors: H
authors: Wang
authors: Ian Y
authors: IY
authors: Chen
authors: Lina
authors: L
authors: He
authors: Joseph C
authors: JC
authors: Wu
authors: Zi-bo
authors: ZB
authors: Li
authors: Khalid A
authors: KA
authors: Mohamedali
authors: Sehoon
authors: S
authors: Kim
authors: Michael G
authors: MG
authors: Rosenblum
authors: Xiaoyuan
authors: X
authors: Chen
authors: Sanjiv Sam
authors: SS
authors: Gambhir
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D005260:Female; D007553:Isotope Labeling; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis*
chemical_list: D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; D040262:Receptors, Vascular Endothelial Growth Factor