Improved molecular imaging contrast agent for detection of human thrombus.

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 x 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 (deltaR(1) = 0.77 +/- 0.02 1/s) relative to Gd-DTPA-BOA (deltaR(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.

• Authors: 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
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 50 Issue 2 Pg. 411-6 (Aug 2003) ISSN: 0740-3194 [Print] United States
• PMID: 12876719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Contrast Media
• Oleic Acids
• Phosphatidylethanolamines
• gadolinium diethylene-triamine-pentaacetic acid-bis-oleate
• gadolinium phosphatidylethanolamine-DTPA
• Oleic Acid
• Fibrin
• Gadolinium DTPA

Topics

• Contrast Media
• Fibrin (analysis)
• Gadolinium DTPA (analogs & derivatives)
• Humans
• In Vitro Techniques
• Magnetic Resonance Imaging
• Oleic Acid
• Oleic Acids
• Phosphatidylethanolamines
• Thrombosis (diagnosis)