RT Journal Article
SR Electronic
T1 Imaging of VEGF Receptor in a Rat Myocardial Infarction Model Using PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 667
OP 673
DO 10.2967/jnumed.107.040576
VO 49
IS 4
A1 Rodriguez-Porcel, Martin
A1 Cai, Weibo
A1 Gheysens, Olivier
A1 Willmann, Jürgen K.
A1 Chen, Kai
A1 Wang, Hui
A1 Chen, Ian Y.
A1 He, Lina
A1 Wu, Joseph C.
A1 Li, Zi-bo
A1 Mohamedali, Khalid A.
A1 Kim, Sehoon
A1 Rosenblum, Michael G.
A1 Chen, Xiaoyuan
A1 Gambhir, Sanjiv Sam
YR 2008
UL http://jnm.snmjournals.org/content/49/4/667.abstract
AB 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. Conclusion: 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.