Molecular Coronary MR Imaging of Human Thrombi using EP-2104R, a Fibrin-Targeted Contrast Agent: Experimental Study in a Swine Model

Zusammenfassung

Ziel: Molekulare MR-Bildgebung von humanem, in Patienten entstandenem Thrombusmaterial in einem Schweinemodell einer Koronarthrombose mittels eines fibrinspezifischen Kontrastmittels (EP-2104R, EPIX Pharmaceuticals, Lexington, Massachusetts, USA). Material und Methoden: Ex vivo aus menschlichem Blut erzeugte frische Thromben und Thromben, welche aus Patienten entfernt wurden, wurden katheterinterventionell in die Koronargefäße von neun Hausschweinen injiziert. Die molekulare MR-Bildgebung erfolgte mit einer navigatorgesteuerten EKG-synchronisierten 3D-Inversions-Gradientenechosequenz mit Schwarzblutkontrast, welche vor Thrombusplatzierung, nach Thrombusfreisetzung, aber vor Kontrastmittelgabe und ca. 2 Sunden nach systemischer (i. v.) Kontrastmittelgabe von 4 µmol/kgKG EP-2104R durchgeführt wurde. Die molekulare MR-Bildgebung wurde von 2 Radiologen analysiert und das Kontrast-zu-Rausch-Verhältnis (CNR) der Thromben bestimmt. Ferner wurde die Gd-Konzentration im Thrombus gemessen. Ergebnisse: Vor Thrombusplatzierung und auch nach Thrombusfreisetzung, aber vor Kontrastmittelgabe waren die Thromben nicht erkennbar. Nur auf den MR-Aufnahmen nach Gabe des fibrinspezifischen Kontrastmittels waren alle 10 Thromben (5 frische, ex vivo hergestellte und 5 Patiententhromben) selektiv und mit einem hohen Kontrast sichtbar (CNR > 12). Eine hohe Gd-Konzentration in den Thromben ( > 100 µM) wurde bestimmt. Schlussfolgerung: Das fibrinspezifische Kontrastmittel EP-2104R erlaubt die molekulare MR-Bildgebung von humanem Thrombusmaterial in einem Schweinemodell einer Koronarthrombose.

Abstract

Purpose: The aim of this study was to investigate the use of a fibrin-specific contrast agent (EP-2104R, EPIX Pharmaceuticals, Lexington, Massachusetts, USA) for targeted molecular magnetic resonance (MR) imaging of human clot material removed from patients in a model of coronary thrombosis in swine. Materials and Methods: Freshly ex vivo engineered clots from human blood and human in situ developed clots removed from patients were delivered into the coronary arteries of nine domestic swine. For MR imaging a navigator-gated, free-breathing, cardiac-triggered 3D inversion recovery black-blood gradient echo sequence was performed prior to clot delivery (baseline), after clot delivery but prior to contrast media administration, and two hours after systemic (i. v.) injection of 4 µmol/kg EP-2104R. MR images were analyzed by two investigators and the contrast-to-noise ratio and Gadolinium (Gd) concentration in the clots were assessed. Results: On baseline images and prior to contrast media application no thrombi were visible. Post contrast administration all 10 coronary emboli (five ex vivo engineered clots and five human clots removed from patients) were selectively visualized as white spots with a mean contrast-to-noise ratio to the blood pool and the surrounding tissue of > 12 and a mean Gd concentration of > 100 µM. Conclusion: Molecular MR imaging using the fibrin-targeted contrast agent EP-2104R allows selective visualization of human clot material in a model of coronary thrombosis in swine.

Key words

molecular imaging - arteriosclerosis - cardiac - vascular - MR imaging

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