Preclinical research
Intravascular ultrasound molecular imaging of atheroma components in vivo

This study was presented in part at the American College of Cardiology Scientific Sessions, Atlanta, Georgia, March 17 to 20, 2002.
https://doi.org/10.1016/j.jacc.2003.07.048Get rights and content
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Abstract

Objectives

Our purpose was to quantitate and confirm specific echogenic immunoliposome (ELIP) atheroma component enhancement in vivo.

Background

Targeted ELIPs for ultrasonic detection and staging of active molecular components of endothelium and atheroma have been developed.

Methods

In Yucatan miniswine, the endothelium was injured from one femoral and one carotid artery, and animals were fed a high-cholesterol diet for two months to create various stages of atheroma. Arteries were imaged with intravascular ultrasound (IVUS) 5 and 10 min after ELIP injection (5-mg dose). Anti-intercellular adhesion molecule-1 (ICAM-1), anti-vascular cell adhesion molecule-1 (VCAM-1), anti-fibrin, anti-fibrinogen, and anti-tissue factor (TF) conjugated ELIPs were used, and immunohistochemistry (IHC) confirmed the presence or absence of molecular expression. Two blinded observers determined if each segment was enhanced by ELIP. Three-dimensional image reconstruction and videodensitometric analysis determined the mean gray-scale (MGS) change of the luminal border.

Results

To determine endothelial injury component enhancement, anti-fibrinogen ELIP enhanced exposed fibrin in all arteries (MGS increased 22 ± 5%; 6 arteries; 2 animals). To determine enhancement of molecular components in atherosclerotic arteries, observers detected enhancement 5 min after anti-VCAM, anti-ICAM, anti-TF, anti-fibrin, and anti-fibrinogen conjugated ELIPs. Furthermore, ELIP enhanced atheroma MGS by 39 ± 18% (n = 8). The IHC staining confirmed the expression of respective molecular targets in all enhanced segments.

Conclusions

It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.

Abbreviations

ELIP
echogenic immunoliposome
ICAM-1
intercellular adhesion molecule-1
IHC
immunohistochemistry
IVUS
intravascular ultrasound
M(Ab)
(monoclonal) antibody
MGS
mean gray scale
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PG
phosphatidylglycerol
TF
tissue factor
VCAM-1
vascular cell adhesion molecule-1

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Supported in part by grant no. HL-59586 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, and the Feinberg Cardiovascular Research Institute, Chicago, Illinois.