Improved molecular imaging contrast agent for detection of human thrombus

✍ Scribed by Patrick M. Winter; Shelton D. Caruthers; Xin Yu; Sheng-Kwei Song; Junjie Chen; Brad Miller; Jeff W.M. Bulte; J. David Robertson; Patrick J. Gaffney; Samuel A. Wickline; Gregory M. Lanza

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 201 KB
• Volume: 50
• Category: Article
• ISSN: 0740-3194
• DOI: 10.1002/mrm.10532

✦ Synopsis

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 r~1~ relaxivities (1.5 T) for Gd‐DTPA‐PE (33.7 (s*mM)^‐1^ and 2.48 × 10^6^ (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 R~1~ values at 1.5 T (Δ__R__~1~ = 0.77 ± 0.02 1/s) relative to Gd‐DTPA‐BOA (Δ__R__~1~ = 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. © 2003 Wiley‐Liss, Inc.