Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical

Zhen Yang, Feng Li, Dedipya Yelamanchili, Zihua Zeng, Corina Rosales, Keith A. Youker, Haifa Shen, Mauro Ferrari, John Mahmarian, Henry J. Pownall, Dale J. Hamilton, Zheng Li

Research output: Contribution to journalArticle

Abstract

Abstract Cardiovascular disease is the leading cause of death in the United States, and rupture of high-risk or vulnerable plaques underlies most acute adverse cardiovascular events, that is, myocardial infarction and stroke. Methods to noninvasively detect and quantify the presence of vulnerable atherosclerotic plaques at the molecular/cellular level are highly desirable for timely therapeutic intervention. Currently, intraplaque neovascularization has been considered as a hallmark of unstable, vulnerable atherosclerotic plaques. Here, a high-affinity positron emission tomography (PET) radiotracer is developed targeting vascular endothelial growth factors (VEGFR) based on a clinically used tyrosine kinase inhibitor vandetanib (ZD6474) and its potential for noninvasive detection of vulnerable plaques is tested. The in vivo PET imaging of ApoE?/? mice shows high specificity and sensitivity of the VEGFR-PET radiotracer to vulnerable plaques. A further corroborating test of the imaging potential for clinical application is also conducted on human arterial atherosclerotic lesions. Specific VEGFR-PET radiotracer uptake is observed by vulnerable plaques in the human arterial specimen with confirmed advanced coronary artery disease. This study suggests VEGFR as a valid biomarker for vulnerable plaque detection, and specific VEGFR-PET is effective for noninvasive imaging of plaque vulnerability in at-risk patients.
Original languageEnglish (US)
Journaladvanced therapeutics
Volume2
Issue number8
DOIs
StatePublished - Aug 1 2019

Keywords

  • angiogenesis
  • atherosclerotic
  • positron emission tomography imaging
  • vascular endothelial growth factor receptor
  • vulnerable plaques

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