Antiangiogenic Cancer Therapy: Monitoring with Molecular US and a Clinically Translatable Contrast Agent (BR55)

Pysz, Marybeth A.; Foygel, Kira; Rosenberg, Jarrett; Gambhir, Sanjiv S.; Schneider, Michel; Willmann, Jürgen K.

doi:10.1148/radiol.10091858

Cited by 146 publications

(159 citation statements)

References 40 publications

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“…Deshpande et al invasive molecular imaging approach that allows in vivo assessment of molecular markers of tumor angiogenesis (16)(17)(18). Since contrast agents used for this imaging approach stay within the vascular compartment owing to their diameter of several micrometers ( 19 ), this approach allows exclusive visualization of molecular markers of angiogenesis expressed on tumor vascular endothelial cells.…”

Section: Molecular Imaging: Molecular Profi Ling In Tumor Angiogenesimentioning

confidence: 99%

Tumor Angiogenic Marker Expression Levels during Tumor Growth: Longitudinal Assessment with Molecularly Targeted Microbubbles and US Imaging

Deshpande

Ren²,

Foygel³

et al. 2011

Radiology

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122

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Purpose:To evaluate the use of molecularly targeted microbubbles (MBs) and ultrasonography (US) in the noninvasive assessment of the level of expression of three angiogenic markers, a v b 3 integrin, endoglin, and vascular endothelial growth factor receptor (VEGFR) 2, on tumor vascular endothelial cells in vivo during tumor growth. Materials and Methods:All procedures using laboratory animals were approved by the Institutional Administrative Panel on Laboratory Animal Care. Binding specifi city of three types of targeted MBs (MB Integrin , MB Endoglin , MB VEGFR2 ) was tested in cell culture under fl ow shear stress conditions. In vivo targeted contrast material-enhanced US imaging signal using the three MB types was measured at three tumor stages (small, medium, large) in three subcutaneous cancer xenografts (breast, ovarian, pancreatic cancer) in mice ( n = 54). In vivo US imaging signal was correlated with ex vivo angiogenic marker expression. Signifi cant differences were evaluated by using the Student t , analysis of variance, Wilcoxon, and Tukey Honest Signifi cant Difference tests. Results:Cell attachment of all three MB types was signifi cantly ( P = .016) higher compared with control MBs, and this attachment could be signifi cantly ( P = .026) decreased by blocking antibodies. Angiogenic marker-expressing cells bound signifi cantly ( P = .003) more targeted MBs than negative control cells, and MB attachment signifi cantly ( P , .001) correlated with marker expression levels on cells ( r = 0.87). In early stage breast and ovarian cancers, in vivo targeted contrastenhanced US demonstrated signifi cantly ( P Յ .04) higher endoglin expression than both a v b 3 integrin and VEGFR2 expression, whereas in early stage pancreatic cancer, marker expressions were not signifi cantly different ( P Ն .07). There was good correlation ( r Ն 0.63; P Յ .05) between in vivo targeted contrast-enhanced US imaging signals using the three MB types and ex vivo immunoblotting results regarding expression levels of the three angiogenic markers. Immunofl uorescence confi rmed expression of a v b 3 integrin, endoglin, and VEGFR2 on tumor vascular endothelial cells. Conclusion:Targeted contrast-enhanced US imaging allows noninvasive in vivo assessment of the expression levels of a v b 3 integrin, endoglin, and VEGFR2, which vary during tumor growth in subcutaneous cancer xenografts.

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Section: Molecular Imaging: Molecular Profi Ling In Tumor Angiogenesimentioning

confidence: 99%

Tumor Angiogenic Marker Expression Levels during Tumor Growth: Longitudinal Assessment with Molecularly Targeted Microbubbles and US Imaging

Deshpande

Ren²,

Foygel³

et al. 2011

Radiology

Self Cite

122

116

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“…Willmann's group also investigated the potential of dual targeted agents for aVb3 and VEGFR-2 showing improved in vivo visualization of tumour angiogenesis in a mouse model of ovarian cancer [101]. Recently, they have further demonstrated the potential of high-frequency molecular imaging using a clinically translatable MB (BR-55, Bracco Inc.) that replaces the strepavadin-biotin linker with a small heterodimeric peptide that targets VEGFR-2 [102]. Results in cell culture and mouse tumours bode well that this may be the first targeted ultrasound contrast agent for the clinic [102].…”

Section: Molecular Imaging Of Angiogenesismentioning

confidence: 99%

Micro-ultrasound for preclinical imaging

2011

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Over the past decade, non-invasive preclinical imaging has emerged as an important tool to facilitate biomedical discovery. Not only have the markets for these tools accelerated, but the numbers of peer-reviewed papers in which imaging end points and biomarkers have been used have grown dramatically. High frequency 'micro-ultrasound' has steadily evolved in the post-genomic era as a rapid, comparatively inexpensive imaging tool for studying normal development and models of human disease in small animals. One of the fundamental barriers to this development was the technological hurdle associated with high-frequency array transducers. Recently, new approaches have enabled the upper limits of linear and phased arrays to be pushed from about 20 to over 50 MHz enabling a broad range of new applications. The innovations leading to the new transducer technology and scanner architecture are reviewed. Applications of preclinical micro-ultrasound are explored for developmental biology, cancer, and cardiovascular disease. With respect to the future, the latest developments in high-frequency ultrasound imaging are described.

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“…These binding ligands can either be coupled to the microbubbles using non-covalent attachment, or chemical conjugation (Klibanov 2005), or they can be integrated into the microbubble shell directly during the production process or after manufacturing (Pochon, Tardy et al 2010;Pysz, Foygel et al 2010). …”

Section: Dynamic Contrast-enhanced Ultrasoundmentioning

confidence: 99%

Molecular Imaging of Tumor Angiogenesis

McDermott¹,

Guimaraes²

2012

Molecular Imaging

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Antiangiogenic Cancer Therapy: Monitoring with Molecular US and a Clinically Translatable Contrast Agent (BR55)

Abstract: Human MB(KDR) allow in vivo imaging and longitudinal monitoring of VEGFR2 expression in human colon cancer xenografts.

Cited by 146 publications

References 40 publications

Tumor Angiogenic Marker Expression Levels during Tumor Growth: Longitudinal Assessment with Molecularly Targeted Microbubbles and US Imaging

Tumor Angiogenic Marker Expression Levels during Tumor Growth: Longitudinal Assessment with Molecularly Targeted Microbubbles and US Imaging

Micro-ultrasound for preclinical imaging

Molecular Imaging of Tumor Angiogenesis

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