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

Research output: Contribution to journalArticle

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

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

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Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical. / Yang, Zhen; Li, Feng; Yelamanchili, Dedipya; Zeng, Zihua; Rosales, Corina; Youker, Keith A.; Shen, Haifa; Ferrari, Mauro; Mahmarian, John; Pownall, Henry J.; Hamilton, Dale J.; Li, Zheng.

In: advanced therapeutics, Vol. 2, No. 8, 01.08.2019.

Research output: Contribution to journalArticle

Harvard

Yang, Z, Li, F, Yelamanchili, D, Zeng, Z, Rosales, C, Youker, KA, Shen, H, Ferrari, M, Mahmarian, J, Pownall, HJ, Hamilton, DJ & Li, Z 2019, 'Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical' advanced therapeutics, vol. 2, no. 8. https://doi.org/10.1002/adtp.201900005

APA

Yang, Z., Li, F., Yelamanchili, D., Zeng, Z., Rosales, C., Youker, K. A., ... Li, Z. (2019). Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical. advanced therapeutics, 2(8). https://doi.org/10.1002/adtp.201900005

Vancouver

Yang Z, Li F, Yelamanchili D, Zeng Z, Rosales C, Youker KA et al. Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical. advanced therapeutics. 2019 Aug 1;2(8). https://doi.org/10.1002/adtp.201900005

Author

Yang, Zhen ; Li, Feng ; Yelamanchili, Dedipya ; Zeng, Zihua ; Rosales, Corina ; Youker, Keith A. ; Shen, Haifa ; Ferrari, Mauro ; Mahmarian, John ; Pownall, Henry J. ; Hamilton, Dale J. ; Li, Zheng. / Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical. In: advanced therapeutics. 2019 ; Vol. 2, No. 8.

BibTeX

@article{63d3d5ac93204e509a3381892b0973a0,
title = "Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical",
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.",
keywords = "angiogenesis, atherosclerotic, positron emission tomography imaging, vascular endothelial growth factor receptor, vulnerable plaques",
author = "Zhen Yang and Feng Li and Dedipya Yelamanchili and Zihua Zeng and Corina Rosales and Youker, {Keith A.} and Haifa Shen and Mauro Ferrari and John Mahmarian and Pownall, {Henry J.} and Hamilton, {Dale J.} and Zheng Li",
note = "doi: 10.1002/adtp.201900005",
year = "2019",
month = "8",
day = "1",
doi = "10.1002/adtp.201900005",
language = "English (US)",
volume = "2",
journal = "advanced therapeutics",
publisher = "Wiley",
number = "8",

}

RIS

TY - JOUR

T1 - Vulnerable Atherosclerotic Plaque Imaging by Small-Molecule High-Affinity Positron Emission Tomography Radiopharmaceutical

AU - Yang, Zhen

AU - Li, Feng

AU - Yelamanchili, Dedipya

AU - Zeng, Zihua

AU - Rosales, Corina

AU - Youker, Keith A.

AU - Shen, Haifa

AU - Ferrari, Mauro

AU - Mahmarian, John

AU - Pownall, Henry J.

AU - Hamilton, Dale J.

AU - Li, Zheng

N1 - doi: 10.1002/adtp.201900005

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - angiogenesis

KW - atherosclerotic

KW - positron emission tomography imaging

KW - vascular endothelial growth factor receptor

KW - vulnerable plaques

U2 - 10.1002/adtp.201900005

DO - 10.1002/adtp.201900005

M3 - Article

VL - 2

JO - advanced therapeutics

T2 - advanced therapeutics

JF - advanced therapeutics

IS - 8

ER -

ID: 55899402