Improved molecular imaging contrast agent for detection of human thrombus

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Abstract
Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus‐specific agent. Effective molecular imaging has been previously demonstrated with fibrin‐targeted Gd‐DTPA‐bis‐oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin‐targeted paramagnetic formulation, Gd‐DTPA‐phosphatidylethanolamine (PE), was compared with Gd‐DTPA‐BOA at 0.05‐4.7 T. Ion‐ and particle‐based r1 relaxivities (1.5 T) for Gd‐DTPA‐PE (33.7 (s*mM)‐1 and 2.48 × 106 (s*mM)‐1, respectively) were about twofold higher than for Gd‐DTPA‐BOA, perhaps due to faster water exchange with surface gadolinium. Gd‐DTPA‐PE nanoparticles bound to thrombus surfaces via anti‐fibrin antibodies (1H10) induced 72% ± 5% higher change in R1 values at 1.5 T (ΔR1 = 0.77 ± 0.02 1/s) relative to Gd‐DTPA‐BOA (ΔR1 = 0.45 ± 0.02 1/s). These studies demonstrate marked improvement in a fibrin‐specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack. Magn Reson Med 50:411–416, 2003.