Improved molecular imaging contrast agent for detection of human thrombus

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

doi:10.1002/mrm.10532

Improved molecular imaging contrast agent for detection of human thrombus

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

172 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	411-416
Number of pages	6
Journal	Magnetic resonance in medicine
Volume	50
Issue number	2
DOIs	https://doi.org/10.1002/mrm.10532
State	Published - Aug 1 2003

Keywords

Contrast agent
Fibrin
Molecular imaging
Nanoparticle
Vulnerable plaque

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1002/mrm.10532

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title = "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 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.",

keywords = "Contrast agent, Fibrin, Molecular imaging, Nanoparticle, Vulnerable plaque",

author = "Winter, {Patrick M.} and Caruthers, {Shelton D.} and Xin Yu and Song, {Sheng Kwei} and Junjie Chen and Brad Miller and Bulte, {Jeff W.M.} and Robertson, {J. David} and Gaffney, {Patrick J.} and Wickline, {Samuel A.} and Lanza, {Gregory M.}",

year = "2003",

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doi = "10.1002/mrm.10532",

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T1 - Improved molecular imaging contrast agent for detection of human thrombus

AU - Winter, Patrick M.

AU - Caruthers, Shelton D.

AU - Yu, Xin

AU - Song, Sheng Kwei

AU - Chen, Junjie

AU - Miller, Brad

AU - Bulte, Jeff W.M.

AU - Robertson, J. David

AU - Gaffney, Patrick J.

AU - Wickline, Samuel A.

AU - Lanza, Gregory M.

PY - 2003/8/1

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N2 - 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.

AB - 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.

KW - Contrast agent

KW - Fibrin

KW - Molecular imaging

KW - Nanoparticle

KW - Vulnerable plaque

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ER -

Improved molecular imaging contrast agent for detection of human thrombus

Abstract

Keywords

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