Imaging of VEGF receptor in a rat myocardial infarction model using PET.
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.
Rodriguez-Porcel
Martin
M
Molecular Imaging Program at Stanford, Department of Radiology, Division of Nuclear Medicine, Stanford University, Stanford, CA 94305-5427, USA.
Cai
Weibo
W
Gheysens
Olivier
O
Willmann
Jürgen K
JK
Chen
Kai
K
Wang
Hui
H
Chen
Ian Y
IY
He
Lina
L
Wu
Joseph C
JC
Li
Zi-bo
ZB
Mohamedali
Khalid A
KA
Kim
Sehoon
S
Rosenblum
Michael G
MG
Chen
Xiaoyuan
X
Gambhir
Sanjiv Sam
SS
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*
D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; D040262:Receptors, Vascular Endothelial Growth Factor