¹⁸F-4V for PET¨CCT Imaging of VCAM-1 Expression in Atherosclerosis

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• 作者：Matthias Nahrendorf ; MD ; PhD^?/sup> ; ^&dagger ; ; ^&Dagger ; ; Edmund Keliher ; PhD^?/sup> ; ^&dagger ; ; Peter Panizzi ; PhD^&dagger ; ; Hanwen Zhang ; PhD^&dagger ; ; Sheena Hembrador ; BS^&dagger ; ; Jose-Luiz Figueiredo ; MD^?/sup> ; ^&dagger ; ; Elena Aikawa ; MD^&dagger ; ; Kimberly Kelly ; PhD^&dagger ; ; Peter Libby ; MD^&Dagger ; ; ^§ ; ; Ralph Weissleder ; MD ; PhD^?/sup> ; ^&dagger ; ; ^&Dagger ; ; ^{rweissleder@mgh.harvard.edu}
• 关键词：atherosclerosis ; inflammation ; molecular imaging ; PET-CT ; VCAM-1
• 刊名：JACC: Cardiovascular Imaging
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：2
• 期：10
• 页码：1213-1222
• 全文大小：1748 K

文摘

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lass=""h4"">Objectives

The aim of this study was to iteratively develop and validate an ¹⁸F-labeled small vascular cell adhesion molecule (VCAM)-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by positron emission tomography¨Ccomputed tomography (PET-CT) in murine atherosclerotic arteries.

lass=""h4"">Background

Hybrid PET-CT imaging allows simultaneous assessment of atherosclerotic lesion morphology (CT) and may facilitate early risk assessment in individual patients. The early induction, confinement of expression to atherosclerotic lesions, and accessible position in proximity to the blood pool render the adhesion molecule VCAM-1 an attractive imaging biomarker for inflamed atheroma prone to complication.

lass=""h4"">Methods

A cyclic, a linear, and an oligomer affinity peptide, internalized into endothelial cells by VCAM-1¨Cmediated binding, were initially derivatized with DOTA to determine their binding profiles and pharmacokinetics. The lead compound was then ¹⁸F-labeled and tested in atherosclerotic apoE^{??/sup> mice receiving a high-cholesterol diet as well as wild type murine models of myocardial infarction and heart transplant rejection.}

lass=""h4"">Results

The tetrameric peptide had the highest affinity and specificity for VCAM-1 (97 % inhibition with soluble VCAM-1 in vitro). In vivo PET-CT imaging using ¹⁸F-4V showed 0.31 ¡À 0.02 SUV in murine atheroma (ex vivo % IDGT 5.9 ¡À 1.5). ¹⁸F-4V uptake colocalized with atherosclerotic plaques on Oil Red O staining and correlated to mRNA levels of VCAM-1 measured by quantitative reverse transcription polymerase chain reaction (R = 0.79, p = 0.03). Atherosclerotic mice receiving an atorvastatin-enriched diet had significantly lower lesional uptake (p < 0.05). Furthermore, ¹⁸F-4V imaging in myocardial ischemia after coronary ligation and in transplanted cardiac allografts undergoing rejection showed high in vivo PET signal in inflamed myocardium and good correlation with ex vivo measurement of VCAM-1 mRNA by quantitative polymerase chain reaction.

lass=""h4"">Conclusions

¹⁸F-4V allows noninvasive PET-CT imaging of VCAM-1 in inflammatory atherosclerosis, has the dynamic range to quantify treatment effects, and correlates with inflammatory gene expression.