Improved molecular imaging contrast agent for detection of human thrombus

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 x 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 1.5T 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.