title: Influence of repetitive contrast agent injections on functional and molecular ultrasound measurements.
abstract: Quantitative contrast-enhanced ultrasound plays an important role in tumor characterization and treatment assessment. Besides established functional ultrasound techniques, ultrasound molecular imaging using microbubbles targeted to disease-associated markers is increasingly being applied in pre-clinical studies. Often, repeated injections of non-targeted or targeted microbubbles during the same imaging session are administered. However, the influence of repeated injections on the accuracy of the quantitative data is unclear. Therefore, in tumor-bearing mice, we investigated the influence of multiple injections of non-targeted microbubbles (SonoVue) on time to peak and peak enhancement in liver and tumor tissue and of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agents (MicroMarker) on specific tumor accumulation. We found significantly decreasing values for time to peak and a tendency for increased values for peak enhancement after multiple injections. Repeated injections of VEGFR2-targeted microbubbles led to significantly increased tumor accumulation, which may result from the exposure of additional binding sites at endothelial surfaces caused by mechanical forces from destroyed microbubbles.
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Rix
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany; Academic Radiology Baden-Baden, Diagnostic and Interventional Radiology, University Medical Center Heidelberg, Baden-Baden, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Pneumology and Critical Care Medicine, Thoraxklinik Heidelberg, Heidelberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Palmowski
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany. Electronic address: fkiessling@ukaachen.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bzyl
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D007089:Image Enhancement / Q000379:methods; D007267:Injections; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D010743:Phospholipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013459:Sulfur Hexafluoride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D040301:Vascular Endothelial Growth Factor Receptor-2; D013459:Sulfur Hexafluoride
keywords: Cancer; Contrast-enhanced ultrasound; Molecular ultrasound; Multiple injections; Peak enhancement; Quantitative imaging; Reproducibility; SonoVue; Time to peak; VEGFR2; Vascular endothelial growth factor receptor 2