Ultrasound molecular imaging of E-selectin in tumor vessels using poly n-butyl cyanoacrylate microbubbles covalently coupled to a short targeting peptide

• Verfasst von: Fokong, Stanley [VerfasserIn]
• Verfasst von: Fragoso, Ana [VerfasserIn]
• Verfasst von: Rix, Anne [VerfasserIn]
• Verfasst von: Curaj, Adelina [VerfasserIn]
• Verfasst von: Wu, Zhuojun [VerfasserIn]
• Verfasst von: Lederle, Wiltrud [VerfasserIn]
• Verfasst von: Iranzo, Olga [VerfasserIn]
• Verfasst von: Gätjens, Jessica [VerfasserIn]
• Verfasst von: Kiessling, Fabian [VerfasserIn]
• Verfasst von: Palmowski, Moritz [VerfasserIn]
• Titel: Ultrasound molecular imaging of E-selectin in tumor vessels using poly n-butyl cyanoacrylate microbubbles covalently coupled to a short targeting peptide
• Verf.angabe: Stanley Fokong, MSc, Ana Fragoso, MS, Anne Rix, BTA, Adelina Curaj, MD, Zhuojun Wu, MSc, Wiltrud Lederle, PhD, Olga Iranzo, PhD, Jessica Gätjens, PhD, Fabian Kiessling, MD, and Moritz Palmowski, MD, PD
• Jahr: 2013
• Umfang: 8 S.
• Fussnoten: Gesehen am 02.03.2022
• Titel Quelle: Enthalten in: Investigative radiology
• Ort Quelle: Philadelphia, Pa. : Lippincott Williams & Wilkins, 1966
• Jahr Quelle: 2013
• Band/Heft Quelle: 48(2013), 12, Seite 843-850
• ISSN Quelle: 1536-0210
• DOI: doi:10.1097/RLI.0b013e31829d03ec
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1790032784

Abstract

The purposes of this study were the development and preclinical evaluation of clinically translatable E-selectin-specific ultrasound contrast agents based on a peptide ligand with the recognition sequence IELLQAR. - The E-selectin-specific peptide was synthesized through solid phase peptide synthesis and covalently attached to poly n-butylcyanoacrylate-stabilized microbubbles with an air core. Quantification of the microbubble surface coverage with peptides was performed through flow cytometry. Targeted adhesion of peptide-coated microbubbles was investigated in vitro using parallel plate flow chamber assays on tumor necrosis factor-α-stimulated human umbilical vein endothelial cells. In vivo imaging was performed in nude mice bearing human ovarian carcinoma xenografts (MLS), followed by ex vivo immunohistochemistry validation of E-selectin expression. - Success of peptide synthesis was validated through preparative reverse phase high-pressure liquid chromatography and electronspray ionization-mass spectrometry. Results of the flow cytometry revealed approximately 4000 E-selectin-specific peptides/microbubble surface. Results of the in vitro experiments demonstrated the specificity of peptide-coated microbubbles to E-selectin (1.10 ± 0.48 vs 0.19 ± 0.09 bound microbubbles per cell, before and after competition respectively; P < 0.01). The in vivo imaging enabled specific assessment of E-selectin expression in MLS carcinoma xenografts (5.21 ± 3.41 vs 1.37 ± 0.67 contrast intensity before and after competition, respectively; P < 0.05). - Clinically translatable microbubbles that were covalently coupled to the short E-selectin-specific peptide (IELLQAR) enabled specific imaging of the E-selectin expression in tumor vessels in vivo.