Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques.
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.


RESULTS
The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd(3+) 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 approximately 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.
Flacke
S
S
Radiologische Klinik, Universität Bonn, Bonn, Germany.
Fischer
S
S
Scott
M J
MJ
Fuhrhop
R J
RJ
Allen
J S
JS
McLean
M
M
Winter
P
P
Sicard
G A
GA
Gaffney
P J
PJ
Wickline
S A
SA
Lanza
G M
GM
D000818:Animals; D001161:Arteriosclerosis / Q000175:diagnosis / Q000378:metabolism; D019921:Biotinylation; D003287:Contrast Media; D004285:Dogs; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D005466:Fluorocarbons; D006801:Humans; D007089:Image Enhancement; D007601:Jugular Veins; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D013927:Thrombosis / Q000175:diagnosis* / Q000378:metabolism; D020246:Venous Thrombosis / Q000175:diagnosis
D003287:Contrast Media; D005466:Fluorocarbons; D005337:Fibrin