title: Molecular ultrasound imaging using contrast agents targeting endoglin, vascular endothelial growth factor receptor 2 and integrin.
abstract: Expression levels of endoglin, αv integrin and vascular endothelial growth factor receptor 2 (VEGFR2) were investigated using targeted, contrast-enhanced ultrasonography in murine melanoma tumor models. Microvasculature and expression levels of biomarkers were investigated using specific contrast agents conjugated with biotinylated monoclonal antibodies. Ultrasound signal intensity from bound contrast agents was evaluated in two groups of mice: control mice and mice treated with sorafenib. Expression levels were analyzed by immunohistochemistry. Endoglin biomarkers were more highly expressed than αv integrin and VEGFR2. Endoglin decreased in the sorafenib group, whereas it tended to increase with time in the control group. Targeted ultrasound contrast agents may be used for non-invasive longitudinal evaluation of tumor angiogenesis during tumor growth or therapeutic treatment in preclinical studies. Endoglin protein, which plays an important role in angiogenesis, seems to be a target of interest for detection of cancer and for prediction of therapeutic efficacy.
authors.affiliation: IR4 M, UMR 8081, Paris-Sud University, CNRS, Orsay, France. Electronic address: ingrid.leguerney@gustaveroussy.fr.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Leguerney
authors.affiliation: Anipath, Faculté Laennec, Université Lyon 1, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.affiliation: Anipath, Faculté Laennec, Université Lyon 1, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gadot
authors.affiliation: Département d'anatomie et de cytologie pathologiques, Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Robin
authors.affiliation: Département d'anatomie et de cytologie pathologiques, Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Pénault-Llorca
authors.affiliation: IR4 M, UMR 8081, Paris-Sud University, CNRS, Orsay, France.
authors.forename: Steeve
authors.initials: S
authors.lastname: Victorin
authors.affiliation: IR4 M, UMR 8081, Paris-Sud University, CNRS, Orsay, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lassau
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D000071063:Endoglin; D005260:Female; D039564:Integrin alphaV / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D000071063:Endoglin; C502004:Eng protein, mouse; D039564:Integrin alphaV; D047908:Intracellular Signaling Peptides and Proteins; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Endoglin; Integrin; Molecular imaging; Targeted ultrasound contrast agents; Vascular endothelial growth factor receptor 2