Collagen imaging with EP-3533 can assess reduction of liver fibrosis with EDP-305 treatment in BDL rats (B-C). Peak liver signal enhancement (%ΔSI) post injection of EP-2104R is significantly higher for DEN animals compared to PBS controlsĬhemical structure of the Type I collagen-binding probes EP-3533, CM-101 and llagen1 (A). False color overlay represents subtraction image of pre-contrast image from the 1-minute post EP-2104R image. T 1-weighted axial images of rats dosed with PBS (left), with DEN and imaged 7 days after fourth DEN dose (center), and imaged 1 day after fourth DEN dose (right). EP-2104R enhanced MRI of injured rat liver ( E, Figure and caption adapted from reference ). C and D, figures and caption adapted from. Corresponding histology and immunohistochemistry (D, bottom row) show the formation of an advanced remodeled thrombus, with low signal of fibrin-specific antibody (D, bottom right) with significant expression of elastin and collagen fibers in areas adjacent to the thrombus (D, bottom left and center), indicating that remodeling took place. After 4 weeks of angiotensin II infusion, the EP-2104R enhanced MRI scan shows a weak-to-moderate signal enhancement at the location of the fibrin-rich thrombus (D, top right, red arrows). Corresponding histology (C, bottom left and center) and immunohistochemistry (C, bottom right) show the formation of a fresh fibrin-rich thrombus with a strong signal using a fibrin-specific antibody. On the EP-2104R enhanced MRI, a strong signal enhancement was measured at the location of the fibrin-rich thrombus (C, top left, red arrows).
On pre-contrast agent scans and control scans with Gd-DTPA (C and D top left and center columns), no significant enhancement was measured.
Visualization of early (2 weeks, C) and advanced/remodeled (4 weeks, D) AAA-associated thrombi by EP-2104R enhanced MRI.
T 1 relaxivity of EP-2104 R in PBS (filled triangle), in the presence of 30 μM fibrinogen (hollow circle) or in the presence of 30 μM fibrin (filled circle) (B, figure and caption adapted from ).
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