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 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.affiliation: Cardiovascular MR Laboratories, Department of Medicine, Cardiovascular Division, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Winter
authors.forename: Shelton D
authors.initials: SD
authors.lastname: Caruthers
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Brad
authors.initials: B
authors.lastname: Miller
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Gaffney
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
mesh_terms: D003287:Contrast Media; D005337:Fibrin / Q000032:analysis; D019786:Gadolinium DTPA / Q000031:analogs & derivatives*; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D019301:Oleic Acid; D009829:Oleic Acids; D010714:Phosphatidylethanolamines; D013927:Thrombosis / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D009829:Oleic Acids; D010714:Phosphatidylethanolamines; C469626:gadolinium diethylene-triamine-pentaacetic acid-bis-oleate; C082531:gadolinium phosphatidylethanolamine-DTPA; D019301:Oleic Acid; D005337:Fibrin; D019786:Gadolinium DTPA