Imaging of VEGF Receptor in a Rat Myocardial Infarction Model Using PET

Journal of Nuclear Medicine

Hui Wang¹  Sehoon Kim¹  Zi-bo Li¹  Ian Y. Chen¹  Sanjiv Sam Gambhir¹  Lina He¹  Joseph C. Wu¹  Khalid A. Mohamedali¹  Martin Rodriguez-Porcel¹  Jürgen K. Willmann¹  Xiaoyuan Chen¹  Michael G. Rosenblum¹  Olivier Gheysens¹  Weibo Cai¹  Kai Chen¹ 

关键词: myocardial infarction;    angiogenesis;    vascular endothelial growth factor (VEGF);    VEGF receptor (VEGFR);    PET;    ⁶⁴Cu;   

DOI  :  10.2967/jnumed.107.040576

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown