Molecular Magnetic Resonance Imaging of Coronary Thrombosis and Pulmonary Emboli With a Novel Fibrin-Targeted Contrast Agent

Abstract

Background-The differential diagnosis of acute chest pain is challenging, especially in patients with normal ECG findings, and may include coronary thrombosis or pulmonary emboli. The aim of this study was to investigate the novel fibrin-specific contrast agent EP-2104R for molecular targeted MR imaging of coronary thrombosis and pulmonary emboli. Methods and Results-Fresh clots were engineered ex vivo from human blood and delivered in the lungs and coronary arteries of 7 swine. Subsequent molecular MR imaging was performed with a navigator-gated free-breathing and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence before and after systemic administration of 7.5 mol/kg EP-2104R. Two swine served as the control group. MR images were analyzed by 2 investigators, and contrast-to-noise ratio and gadolinium concentration in the clots were assessed. Before contrast media application, no thrombi were visible. After contrast administration, all 32 pulmonary emboli, 3 emboli in the right heart, and 5 coronary thrombi were selectively visualized as white spots with a mean contrast-to-noise ratio of 32Ϯ19. The average gadolinium concentration from all 3 types of thrombi was 144Ϯ79 mol/L. Conclusions-Molecular MR imaging with the fibrin-targeted contrast-agent EP-2104R allows selective visualization of acute coronary, cardiac, and pulmonary thrombi.

A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI

“…Conjugation of superparamagnetic particles to antibodies or peptidomimetic peptides has previously been used to selectively image cellular receptors expressed in various disease conditions (11,23,24). Gadolinium-based contrast agents shorten the T 1 relaxation time of protons and provide positive contrast on T 1 -weighted images (25).…”

“…Recent progress in MRI has enabled the detection of such molecular targets by designing contrast agents that bind to cellular receptors or surface antigens (11,12). By delivering high payloads of contrast agent such as iron oxide particles to molecular epitopes, imaging of even sparsely distributed molecules is possible (13,14).…”

Molecular MRI of Cerebral Venous Sinus Thrombosis Using a New Fibrin-Specific MR Contrast Agent

“…In various in vivo studies, it has been used to image human thrombi in the cardiac atrium, coronary or pulmonary vessels, or the carotid arteries. [15][16][17][18][19][20] It has the further advantage of enabling imaging of acute, subacute, and chronic thrombi. 15,19,20 The aim of this study was to investigate the potential of EP-2104R for molecular imaging of sinus thrombosis using a recently developed minimal invasive animal model, 21 with special consideration of the particular anatomical features of cerebral venous and surrounding anatomy.…”

Molecular Imaging in Cardiovascular Diseases

“…It also has a key function in thrombus formation following plaque rupture. In various studies a fibrin-specific low-molecular probe has been successfully employed for imaging thrombi in the jugular vein, aorta, pulmonary arteries as well as in coronary arteries [35,36,50,51]. Compared to conventional compounds such as Gd-DTPA, the probe indicated high sensitivity for the detection of fibrin; this is explained by the high relaxivity of the specific molecular probe.…”