Circulation. 2001;104:1280-1285
doi: 10.1161/hc3601.094303
doi: 10.1161/hc3601.094303
(Circulation. 2001;104:1280.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Novel MRI Contrast Agent for Molecular Imaging of Fibrin
Implications for Detecting Vulnerable Plaques
From the Radiologische Klinik, Universität Bonn, Bonn, Germany (S. Flacke); Philips Medical Systems, Best, Netherlands (S. Fischer); the Department of Medicine, Cardiovascular Division, Washington University Medical School, St Louis, Mo (M.J.S., R.J.F., J.S.A, M.M., P.W., G.A.S., S.A.W., G.M.L.); and the Department of Surgery, St Thomas’s Hospital, London, UK (P.J.G.).
Correspondence to Dr Gregory M. Lanza, Department of Cardiology, Campus Box 8086, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110. E-mail greg{at}cvu.wustl.edu
Background— Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques.
Methods and Results— The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd3+ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL · s-1 · pmol-1 (10% Gd-DTPA nanoparticles) to 0.54 mL · s-1 · pmol-1 for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was 
118±21, and that between the targeted clot and the control clot was 131±37.
Conclusions— These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.
Key Words: magnetic resonance imaging • contrast media • plaque • fibrin
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