title: Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles.
abstract: MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed forin vivomolecular imaging of cells based on the use of ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Although immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNAin vivo. To visualize the differential FosB gene expression profilein vivoafter burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets viain vivohybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using systemic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene delivery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcriptionin vivo, in a clinically relevant mouse model of burn injury for the first time.
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA.
authors.forename: Aristarchos
authors.initials: A
authors.lastname: Papagiannaros
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA ; Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA ; Department of Biochemistry "G. Moruzzi", University of Bologna, Bologna, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.affiliation: Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Day
authors.affiliation: Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School and Massachusetts General Hospital, Boston, USA ; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.affiliation: Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Liu
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA ; Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA ; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: A Aria
authors.initials: AA
authors.lastname: Tzika
keywords: Burn; C-Fos; Positive Contrast; Skeletal Muscle; Superparamagnetic Iron-Oxide (Uspio); Transverse Relaxation in the Rotating Frame (T2r)