Developing VEGF receptors targeted molecular probes for PET imaging of vulnerable atherosclerotic plaques

Zhen Yang, Feng Li, Zheng Li

Research output: Contribution to journalArticle

Abstract

1526Background: Rupture of unstable plaques may lead to acute myocardial infarction and sudden cardiac death, which remains the leading cause of morbidity and mortality in western countries. Thus, it is highly desirable for identifying these vulnerable plaques before the rupture occurs. Objectives: Study of atherosclerotic plaque reveals a strong correlation between plaque angiogenesis and plaque progression. Therefore, we assume angiogenesis growth factors, such as vascular endothelial growth factor (VEGF), could be used as new targets for imaging vulnerable plaques. Methods: Vandetanib ligand (also named ZD6474) was used to develop a dimer tracer for targeting VEGF receptors. Apolipoprotein E-efficient (ApoE-/-) mouse was used to develop atherosclerotic lesions in the aorta. Upon labelled with 89Zr radiotracers, the dimer tracer was injected into the modeled mouse to do the in vivo and ex vivo PET imaging of aortic plaques. To further extend our developed probe for clinical potential, we also tested staining of the probe on human left anterior descending artery (LAD) from failing heart, which developed appreciable atherosclerotic lesions. Results: The aortic plaques were specifically visualized by PET imaging. Further pathological studies confirmed the higher expression of VEGF receptors in those plaques exhibiting typical features of plaque vulnerability. Remarkably, our probe also showed extraordinary targeting to the LAD plaques that exhibited high expression of VEGF receptors. Conclusions: It is very encouraging to develop VEGF receptors targeted probes for PET imaging of atherosclerotic plaques. Our developed tracer of ZD6474 dimer shows promising for clinical diagnosis of patients at risk of plaque rupture.
Original languageEnglish (US)
Pages (from-to)1526
Number of pages1
JournalJournal of Nuclear Medicine
Volume59
Issue numbersupplement 1
StatePublished - May 1 2018

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