Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis

High-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble...

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Main Authors: Joshua J. Rychak, James Graba, Alison M.Y. Cheung, Bina S. Mystry, Jonathan R. Lindner, Robert S. Kerbel, F. Stuart Foster
Format: Article
Language:English
Published: SAGE Publishing 2007-09-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2007.00024
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author Joshua J. Rychak
James Graba
Alison M.Y. Cheung
Bina S. Mystry
Jonathan R. Lindner
Robert S. Kerbel
F. Stuart Foster
author_facet Joshua J. Rychak
James Graba
Alison M.Y. Cheung
Bina S. Mystry
Jonathan R. Lindner
Robert S. Kerbel
F. Stuart Foster
author_sort Joshua J. Rychak
collection DOAJ
description High-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble ultrasound contrast agents bearing targeting ligands specific for molecular markers of tumor angiogenesis using high-frequency microultrasound imaging. A xenograft tumor model in the mouse was used to image vascular endothelial growth factor receptor 2 (VEGFR-2) expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal antibody or an isotype control. Microultrasound imaging was accomplished at a center frequency of 40 MHz, which provided lateral and axial resolutions of 40 and 90 μm, respectively. The B-mode (two-dimensional mode) acoustic signal from microbubbles bound to the molecular target was determined by an ultrasound-based destruction-subtraction scheme. Quantification of the adherent microbubble fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2-targeted microbubbles relative to control-targeted microbubbles. These data demonstrate that contrast-enhanced microultrasound imaging is a useful method for assessing molecular expression of tumor angiogenesis in mice at high resolution.
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spelling doaj-art-00187e3682624f2cb29545263a1daed52025-01-03T00:10:25ZengSAGE PublishingMolecular Imaging1536-01212007-09-01610.2310/7290.2007.0002410.2310_7290.2007.00024Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor AngiogenesisJoshua J. RychakJames GrabaAlison M.Y. CheungBina S. MystryJonathan R. LindnerRobert S. KerbelF. Stuart FosterHigh-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble ultrasound contrast agents bearing targeting ligands specific for molecular markers of tumor angiogenesis using high-frequency microultrasound imaging. A xenograft tumor model in the mouse was used to image vascular endothelial growth factor receptor 2 (VEGFR-2) expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal antibody or an isotype control. Microultrasound imaging was accomplished at a center frequency of 40 MHz, which provided lateral and axial resolutions of 40 and 90 μm, respectively. The B-mode (two-dimensional mode) acoustic signal from microbubbles bound to the molecular target was determined by an ultrasound-based destruction-subtraction scheme. Quantification of the adherent microbubble fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2-targeted microbubbles relative to control-targeted microbubbles. These data demonstrate that contrast-enhanced microultrasound imaging is a useful method for assessing molecular expression of tumor angiogenesis in mice at high resolution.https://doi.org/10.2310/7290.2007.00024
spellingShingle Joshua J. Rychak
James Graba
Alison M.Y. Cheung
Bina S. Mystry
Jonathan R. Lindner
Robert S. Kerbel
F. Stuart Foster
Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
Molecular Imaging
title Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
title_full Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
title_fullStr Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
title_full_unstemmed Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
title_short Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis
title_sort microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis
url https://doi.org/10.2310/7290.2007.00024
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