Abstract
RATIONALE AND OBJECTIVES: Fibrin deposition has been indicated within the stroma of a majority of solid tumors. Here we assess the feasibility of using the established fibrin-specific probe EP-2104R for noninvasive imaging of fibrin in the context of breast cancer. METHODS: EP-2104R, untargeted gadopentetate dimeglumine (Gd-DTPA), and a newly synthesized nonfibrin binding control linear peptide (CLP) were compared using steady-state and dynamic contrast-enhanced magnetic resonance imaging in a breast cancer xenograft mouse model at 9.4 T. RESULTS: EP-2104R transiently enhanced both tumor core and tumor periphery, but only the enhancement in the tumor periphery persisted even 90 minutes after EP-2104R administration. However, untargeted Gd-DTPA and CLP are not retained in the tumor periphery. The half-life of EP-2104R in the tumor periphery (103 ± 18 minutes) is significantly longer (P < 0.05) than that of either Gd-DTPA (29.6 ± 2.4 minutes) or CLP (42.4 ± 1.5 minutes), but the rate of clearance is similar for all the 3 probes from the tumor core. The presence of high concentrations of fibrin in the tumor periphery was corroborated using immunohistochemistry with a fibrin-specific antibody. CONCLUSIONS: The persistent enhancement observed in the tumor periphery with EP-2104R is likely a result of its fibrin-specific binding rather than its size and demonstrates the feasibility of EP-2104R for molecular imaging of fibrin in tumor stroma.