title: MR molecular imaging of thrombus: development and application of a Gd-based novel contrast agent targeting to P-selectin.
abstract: Molecular imaging of thrombus formation at initial stage requires a robust thrombus-specific contrast agent with high sensitivity. In this study, we report a novel P-selectin-targeted paramagnetic molecular imaging agent and the agent's potential to sensitively detect occult microthrombi on the intimal surface of endothelium. Platelet clots and blood clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that was improved with increasing gadolinium level. In vivo contrast enhancement under part of circulation conditions was assessed in dogs. The micro-thrombi around the femoral vein of dog demonstrated higher signal intensities than the control clots and the adjacent muscle. Histology was performed on regions likely to contain thrombus as indicated by MRI. These results suggest that molecular imaging of P-selectin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of P-selectin and may allow for early, direct identification of microthrombi, leading to early diagnosis.
authors.affiliation: Ruijin Hospital and Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Jin
authors.lastname: Tong Zhou
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Zhao
authors.forename: Qiu-Lan
authors.initials: QL
authors.lastname: Ding
authors.forename: Deng-Bin
authors.initials: DB
authors.lastname: Wang
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Zhao
authors.lastname: Jing-Dai
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Wang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Ge
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D002417:Cattle; D003287:Contrast Media / Q000493:pharmacokinetics*; D004285:Dogs; D016503:Drug Delivery Systems; D005268:Femoral Vein / Q000473:pathology*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D021621:Imaging, Three-Dimensional; D018796:Immunoconjugates / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D057054:Molecular Imaging; D053758:Nanoparticles; D019007:P-Selectin / Q000032:analysis* / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D020246:Venous Thrombosis / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D018796:Immunoconjugates; D019007:P-Selectin; C550235:PsL-EGFmAb-BSA4-(Gd-DTPA)n; D012710:Serum Albumin, Bovine; D019786:Gadolinium DTPA