期刊
JOURNAL OF NUCLEAR MEDICINE
卷 49, 期 4, 页码 667-673出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.107.040576
关键词
myocardial infarction; angiogenesis; vascular endothelial growth factor (VEGF); VEGF receptor (VEGFR); PET; Cu-64
资金
- NCI NIH HHS [R21 CA102123, CA114747 P50, P50 CA114747] Funding Source: Medline
- NHLBI NIH HHS [R01 HL078632, 1 R01 HL078632, K99 HL088048-01, K99 HL088048] Funding Source: Medline
- NIBIB NIH HHS [R21 EB001785] Funding Source: Medline
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 (Cu-64-DOTA-VEGF(121) [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, Cu-64-DOTA-VEGF(121) 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 Cu-64-DOTA-VEGF(121) signal was confirmed by CT coregistration and autoradiography. VEGFR specificity of the Cu-64-DOTA-VEGF(121) probe was confirmed by in vivo use of a Cu-64-DOTA-VEGF(mutant). Baseline myocardial uptake of Cu-64-DOTA-VEGF(121) 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 Cu-64-DOTA-VEGF(121) 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.
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