Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles

Aristarchos Papagiannaros, Valeria Righi, George G. Day, Laurence G. Rahme, Philip K. Liu, Alan J. Fischman, Ronald G. Tompkins, A. Aria Tzika

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.
Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School and Massachusetts General Hospital, Boston, USA.
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA.

DOI: 10.4236/ami.2012.24005                

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 for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though 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 mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after 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 via in vivo hybridization. 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 sys- temic 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 nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery 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 transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.

Keywords

Positive Contrast; Transverse Relaxation in the Rotating Frame (T2r); Superparamagnetic Iron-Oxide (Uspio); Burn; Skeletal Muscle; C-Fos

Conflicts of Interest

The authors declare no conflicts of interest.

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