title: VEGFR2-targeted molecular imaging in the mouse embryo: an alternative to the tumor model.
abstract: As a tumor surrogate, the mouse embryo presents as an excellent alternative for examining the binding of angiogenesis-targeting microbubbles and assessing the quantitative nature of molecular ultrasound. We establish the validity of this model by developing a robust method to study microbubble kinetic behavior and investigate the reproducibility of targeted binding in the murine embryo. Vascular endothelial growth factor receptor 2 (VEGFR2)-targeted (MBV), rat immunoglobulin G2 (IgG2) control antibody-targeted (MBC) and untargeted (MBU) microbubbles were introduced into vasculature of living mouse embryos. Non-linear contrast-specific and B-mode ultrasound imaging, performed at 21 MHz with a Vevo-2100 scanner, was used to collect basic perfusion parameters and contrast mean power ratios for all bubble types. We observed a twofold increase (p < 0.001) in contrast mean power ratios for MBV (4.14 ± 1.78) compared with those for MBC (1.95 ± 0.78) and MBU (1.79 ± 0.45). Targeted imaging of endogenous endothelial cell surface markers in mouse embryos is possible with labeled microbubbles. The mouse embryo thus presents as a versatile model for testing the performance of ultrasound molecular targeting, where further development of quantitative imaging techniques may enable rapid evaluations of biomarker expression in studies of vascular development, disease and angiogenesis.
authors.affiliation: Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Electronic address: janet.denbeigh@utoronto.ca.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Denbeigh
authors.affiliation: Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Nixon
authors.affiliation: Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John M
authors.initials: JM
authors.lastname: Hudson
authors.affiliation: Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Mira C
authors.initials: MC
authors.lastname: Puri
authors.affiliation: Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: F Stuart
authors.initials: FS
authors.lastname: Foster
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000196:embryology / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D045423:Microbubbles; D025202:Molecular Diagnostic Techniques / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000196:embryology / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Micro-ultrasound; Microbubble contrast agent; Molecular imaging; Mouse embryo; Vascular endothelial growth factor receptor 2