Ultrasound Contrast Agents For Ultrasound Molecular Imaging

Abstract

Ultrasound is a real-time imaging technique which is widely used in many clinical applications for its capacity to provide anatomic information with high spatial and temporal resolution. The advent of ultrasound contrast agents in combination with contrast-specific imaging modes has given access to perfusion assessments at an organ level, leading to an improved diagnostic accuracy. More recently, the development of biologically-targeted ultrasound contrast agents has expanded the role of ultrasound even further into molecular imaging applications. Ultrasound molecular imaging can be used to visualize the expression of intravascular markers, and to assess their local presence over time and/or during therapeutic treatment. Major applications are in the field of inflammation and neoangiogenesis due to the strictly intravascular presence of microbubbles. Various technologies have been investigated for attaching the targeting moiety to the shell from simple biotin-avidin constructs to more elaborated insertion within the shell through attachment to PEG residues. This important improvement has allowed a clinical translation of initial pre-clinical investigations, opening the way for an early detection and an accurate characterization of lesions in patients. The combination of anatomic, functional and molecular information/data provided by contrast ultrasound is a powerful tool which is still in its infancy due to the lack of agents suitable for clinical use. The advantages of ultrasound techniques combined with the molecular signature of lesions will represent a significant advance in imaging in the field of personalized medicine.

Zusammenfassung

Die Sonografie ist eine weitverbreitete Bildgebungsmethode mit hoher örtlicher und zeitlicher Auflösung. Die Einführung von Ultraschallkontrastmitteln im Zusammenhang mit kontrastmittelspezifischer Software erlaubt die Analyse organspezifischer Durchblutungsmuster und Perfusion mit Verbesserung der diagnostischen Genauigkeit. Die weitere Entwicklung von mit biologischen Markern versehenen Ultraschallkontrastmitteln erlaubt eine molekulare Bildgebung. Die molekulare Bildgebung ermöglicht die Darstellbarkeit der Expression von intravaskulären Markern vor, während und nach medikamentöser Behandlung. Der Vorteil der Ultraschallkontrastmittel liegt in ihrer strikten intravaskulären Verteilung, sodass Neoangiogenese und Entzündungsvorgänge dargestellt werden können. Verschiedene Technologien wurden evaluiert, um das zielgerichtete Molekül an die Kontrastmittelhülle zu binden. Diese reichen von einfachen Biotin-Avidin-Konstrukten bis zu komplizierteren Anheftungen mittels PEG-Abkömmlingen. Aktuelle Fortschritte auf diesem Gebiet erlauben die Übertragung präklinischer Erfahrung für eine verbesserte Detektion und Charakterisierung von Neoplasien und Entzündungsprozessen. Die kombinierte Anwendung und Auswertung anatomischer, funktionsanalytischer und molekularer Informationen im Rahmen der Kontrastmittelsonografie ist vielversprechend steht aber noch in den Anfängen, da bisher nur wenige klinisch relevante Markermoleküle existieren. Die beschriebenen Vorteile der Sonografie kombiniert mit der molekularen Signatur von Neoplasien wird im Rahmen der personalisierten Medizin eine relevante Rolle spielen.

Schlüsselwörter

Mikrobläschen - kontrastverstärkterUltraschall - molekulare Bildgebung - VEGFR2 - Selektine - gastrointestinaler Stromatumor (GIST) - kolorektales Karzinom - gastro-entero-pankreatische Tumoren

Key words

microbubbles - contrast-enhanced ultrasound - molecular imaging - VEGFR2 - selectins - gastrointestinal stromal tumors (GIST) - colorectal cancer - gastro-entero-pancreatic tumors

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